Left ventricular responses to supine bicycle ergometer exercise were studied by gated radionuclide angiocardiography (RNA), in 12 normal subjects (group A), 11 coronary patients without effort angina (group B) and 17 coronary patients with effort angina (group C). In the serial measurement of global ejection fraction (EF) there was a significant increase during peak exercise (PEx) in group A and B. In group C, global EF during mild exercise (MEx) did not increase, but decreased significantly during PEx. There results suggest the necessity of achieving adequate exercise loading in the diagnosis of exercise-induced ischemia, and also, that the serial measurement of global EF during exercise appears to be highly valuable. In the assessment of regional wall motion on the basis of regional EF, abnormal responses to exercise were highly inducible in the anteroseptal region in coronary patients with left anterior descending artery involvement. Abnormal wall motion in the other regions was less indicative for right coronary or left circumflex artery dysfunction. We examined hemodynamic responses to exercise by a Swan-Ganz catheter during RNA study in 5 patients of group A, 5 of group B, and 9 of group C. There was a large increase in left ventricular stroke work index (LVSWI) with a small rise in pulmonary capillary wedge pressure (PCWP) in group A. In group B LVSWI increased with a moderate rise in PCWP during PEx. In group C there was a negligible increase of LVSWI despite a marked rise in PCWP. A similar relationship was present between the LVSWI and the end-diastolic count (EDC) in the left ventricular region of interest. In MEx, however, the rise in PCWP in group C was more prominent than the increase in EDC. Thus, the present data indicate that the left ventricle in group C operates on a steeper portion of the diastolic pressure-volume curve than that in group A or B.

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In order to determine the validity of the left ventricular (LV) diastolic function for evaluation of ischemic heart disease, gated radionuclide angiography was performed in 37 patients with transmural myocardial infarction (MI) [18 : anterior, 19 : inferior infarction] and 10 normal control subjects. LV ejection fraction (LVEF) was decreased in patients with anterior MI but not in those with inferior MI. Time to peak filling rate was not significantly prolonged in both anterior MI and inferior MI. Filling fraction was apparently reduced only in anterior MI. However, peak filling rate (PFR) was significantly reduced even in inferior MI as well as in anterior MI. PER correlated well with LVEF in normal control, anterior MI and inferior MI. In both anterior MI and inferior MI, their coefficients were smaller than in controls. The normal PFR always indicated normal LVEF, while normal LVEF was not necessarily indicative of normal PFR. Results indicated that LV diastolic function estimated by equilibrium radionuclide angiography might reflect more precisely LV dysfunction in old MI than LV systolic function. The reduction of LV diastolic function in old MI was more prominent than that of LV systolic function. Therefore, it may be deduced that evaluation of LV diastolic function is essential to the estimation of the degree of ischemic myocardial cell damage and the efficacy of drugs on ischemia-induced LV dysfunction.

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With use of biplane cine-angiocardiograms, the measurements of right and left ventricular volume were determined in 11 children with transposition of the great arteries following Mustard's procedure. Right ventricular end-diastolic volume (RVEDV) ranged from 124 to 264 percent of the normal right ventricular volume with an average of 188 ± 40 (SDM) percent, and left ventricular end-diastolic volume (LVEDV) ranged from 47 to 181 (122 ±43) percent of the normal (p < 0.01, vs. RVEDV). Right ventricular ejection fraction (RVEF) ranged from 0.26 to 0.66 (0.42 ± 0.11), and left ventricular ejection fraction (LVEF) ranged from 0.51 to 0.79 (0.66 ± 0.09) (p < 0.001, vs RVEF). Left ventriculography showed a deviation of the interventricular septum toward the left ventricle in patients with simple transposition of the great arteries not associated with left ventricular hypertension. The left to right ventricular systolic pressure ratio ranged from 0.22 to 1.02 (0.48 ± 0.28), and the left to right ventricular end-diastolic volume ratio ranged from 0.43 to 1.00 (0.63 0.18). There was a high correlation between the left to right ventricular systolic pressure ratio and the left to right ventricular end-diastolic volume ratio (r=0.94, p < 0.001). The left to right ventricular systolic pressure ratio also correlated well with the right ventricular ejection fraction (r=0.90, p < 0.001). Deviation of the interventricular septum was considered to result in a diminished ejection fraction of the right ventricle, in patients with simple transposition of the great arteries not associated with left ventricular hypertension, after Mustard's procedure.

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The effects of prostacyclin (PGI₂) on alveolar hypoxic pulmonary vasoconstriction were investigated in the conscious adult sheep. In our model, hypoxia also produced increases in pulmonary arterial pressure (P_<PA) and pulmonary vascular resistance (PVR), indicating pulmonary vasoconstriction. PGI₂ was injected rapidly as a 0.5 μg/kg bolus via the right atrium in five sheep during normoxia and hypoxia. During normoxia, PGI₂ increased P_PA and cardiac output, and decreased systemic arterial pressure (P_SA), systemic vascular resistance (SVR) and PVR. Left atrial pressure did not change. During hypoxia following PGI₂ administration, P_PA decreased, CO increased, and PVR decreased, suggesting dilator action on the pulmonary resistance vessels. As the same time P_SA and SVR decreased, suggesting dilator action on the systemic resistance vessels. However, the degree of the decline in PVR caused by PGI₂ was much greater during hypoxia than during normoxia. The decreases in P_SA and SVR induced by PGI₂ were not significant between hypoxia and normoxia. These findings confirm that PGI₂ decreases pulmonary and systemic vascular resistances in normoxic and hypoxic sheep. Moreover, during hypoxia, associated with the increased P_PA and PVR, the administration of PGI₂ appears to be particularly effective in normalizing these parameters.

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It is appreciated that, linked with B-mode echocardiography, the real-time two-dimensional Doppler flow imaging technique provides information on the heart, which has never been available with conventional methods, greatly improving the capabilities of cardiac ultrasound. In general, the concept of major heart disease consists of anatomical abnormalities and those in intracardiac flow condition. The present method provides information on these two aspects simultaneously ; consequently, it is regarded as a closer approach to heart diseases, compared with conventional examinations and techniques. The equipment is also convenient to operate. The combination of real-time two-dimensional Doppler flow imaging and B-mode echocardiography is expected to become a standard tool of the ultrasound examination of the heart.

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The validity of X-ray CT in the functional diagnosis of several cardiovascular diseases was evaluated. CT was useful for assessing the amount and the characteristics of intrapericardial fluid, and it was also useful for the diagnosis of cardiac tamponade and constictive pericarditis. A dynamic scan was found to be useful for determining the location, direction and the magnitude of intracardiac shunts, and for differentiating the true lumen from the false lumen in dissecting aortic aneurysms. As direct evidence of myocardial infarction, a filling defect in the infarcted area and late enhancement of the same area on delayed scan were noted. Regional wall motion abnormalities could be demonstrated by ECG gated CT, and other findings such as myocardial thinning, ventricular aneurysm and mural thrombi in the infarcted area were documented.

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To evaluate function of the left ventricle and myocardial perfusion images, digital subtraction angiography (DSA) was performed in 45 patients with ischemic heart disease. Validity of the technique was compared with data obtained from cine left ventriculogram in all patients and 201 Tl myocardial images in 20 patients. End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) calculated from DSA were correlated closely with those from cine left ventriculogram (r=0.92, r=0.94 and 4=0.86, respectively). Regional contractility at the antero-lateral wall of the left ventricle, assessed by DSA, was also correlated well with cine left ventriculogram (r=0.75). Evaluation of the inferior wall motion showed less correlation in both procedures (r=0.68). Phase and amplitude analysis with the same technique with radionuclide cardiac angiography was successfully applied in left ventriculogram obtained by DSA. The procedure seems to be helpful for objective evaluation of the left ventricular wall motion. Myocardial perfusion image, obtained with modified Radtke's technique, showed good coincidence with 201 Tl images. Thus, DSA is applicable for evaluation of function of the left ventricle and myocardial perfusion in patients with ischemic heart disease.

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Positron emission computed tomography (PET) offers regional measurement of physiological and biochemical processes in vivo. We have constructed a whole-body multislice PET scanner, which provides 7 tomographic images at 16 mm intervals simultaneously. The high sensitivity with good spatial resolution of this system permits dynamic studies of the heart. PET scan of the heart was performed following intravenous bolus injection of <13>^N labeled ammonia. Serial dynamic images in normal cases showed early accumulation of tracer in the myocardium and rapid clearance from the cardiac blood pool. Delayed clearance from the blood and prolonged retention in the dorsal part of the lungs were observed in cases with myocardial infarction. A perfusion defect was clearly visualized in myocardial infarction except for infarction of the inferior wall. Transient ischemia was also visualized with exercise loading. Thus, PET with ¹³N ammonia is a valuable diagnostic tool for the evaluation of regional myocardial perfusion in coronary artery disease.

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In 36 patients with effort angina pectoris without myocardial infarction, the sites of exercise-induced ST changes (depression and elevation) on the body surface were investigated. Exercise-induced ST depression was most often seen in left anterior chest leads. The body surface distribution of ST depression failed to identify the obstructed coronary artery. Exercise-induced myocardial ischemia was thought to extend to the greater part of the subendocardial region of the left ventricle. Exercise-induced ST elevation was mainly found on the upper right anterior chest. It has been suggested that these leads face the interior of the left ventricle and the observed ST elevation directly reflects subendocardial ischemia of the left ventricle. This data is important for evaluating ST changes in exercise electrocardiography.

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We have developed anticardiac myosin antibodies, especially monoclonal antibodies, for helping in the diagnosis of heart disease. Our investigations were divided into three research projects. 1. We visualized the distribution of myosin isozymes in human atrial and ventricular myocardium by an immunofluorescence staining method using monoclonal antibodies specific for individual human cardiac myosin isozymes. We also revealed the redistribution of these cardiac myosin isozymes in an overloaded condition. The isozymic pattern of cardiac myosin was changed from the atrial type to the ventricular type in the overloaded atrium. This isozymic redistribution can be considered as physiological adaptive mechanism to meet increased cardiac work during overload. 2. We developed a new method of imaging for myocardial infarction by single photon emission tomography using labelled monoclonal antibody specific for cardiac myosin heavy chain. Specific localization of the labelled antibody was demonstrated in the infarcted area and no accumulation of radioactivity was shown in the bone matrix as observed in ^99mTc pyrophosphate images. 3. We developed a sensitive radioimmunoassay of cardiac myosin light chain I (LCI) and demonstrated that peak serum levels of LCI in the patients with acute myocardial infarction correlated well with the left ventricular ejection fraction. Furthermore, LCI release from the infarcted myocardium was not affected by coronary reperfusion due to intracoronary thrombolysis. Thus, serial determinations of serum LCI better quantify the extent of myocardial damage even after coronary reperfusion in acute myocardial infarction.

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