In order to investigate left ventricular performance during exercise in patients with myocardial infarction and evaluate the effects of sublingual isosorbide dinitrate (ISDN) on left ventricular performance, we performed a symptom-limited multigraded exercise test using a bicycle ergometer in supine position . Thirty-seven patients with myocardial infarction were evaluated in order to clarify the hemodynamic responses to exercise with and without sublingual ISDN. Patients were subdivided into 3 groups according to the level of pulmonary capillary pressure (PCP) and cardiac index (CI) at peak exercise as follows: Group I (14 patients); PCP < 18 mmHg, CI ≥ 5.0 or CI < 5.0 L/min/m², Group II (11 patients); PCP ≥ 18 mmHg, CI ≥ 5.0 L/min/m², Group III (12 patients); PCP ≥ 18 mmHg, CI < 5.0 L/min/m². Exercise capacity without ISDN (control study) was correlated with left ventricular performance during exercise. Although left ventricular performance in patients who complained of dyspnea or chest pain at peak exercise was worse than those who complained of leg fatigue, we could not predict hemodynamics during exercise from the level of hemodynamic parameters at rest in each patient. Determinant factors of left ventricular performance during exercise were age, previous history of myocardial infarction, the severity of coronary artery lesion and the extent of left ventricular wall motion abnormality which was estimated by left ventriculogram as an index of infarct size. After sublingual ISDN (ISDN study), exercise capacity was improved. No patient terminated exercise because of chest pain and only one did because of dyspnea. While no significant differences in heart rate (HR), mean arterial pressure (MAP) cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) and systemic vascular resistance (SVR) were observed at peak exercise between the control study and ISDN study in Groups I and II, PCP was lower in the ISDN study than in the control study. On the other hand, CI and LVSWI in Group III increased and SVR significantly decreased at peak exercise. Effects of ISDN on hemodynamics during exercise was well related to the severity of coronary artery lesion and inversely correlated with the infarct size. These results indicate that investigation of hemodynamic response to exercise is a useful method for determination of cardiac rehabilitation program in patients with myocardial infarction and ISDN is an effective drug for the improvement of left ventricular performance during exercise.

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Ten patients with effort angina were studied in a randomized double-blind cross-over trial in order to investigate the effect of sustained release propranolol (LA) and conventional propranolol (Prop) formulations on exercise tolerance. LA was given once daily and Prop three times daily. Treadmill exercise tests were performed using the Bruce protocol and the plasma propranolol levels were measured. The following results were obtained: 1) LA proved to have an anti-anginal effect similar to Prop. No adverse reactions were observed after administration of either of the drugs. 2) Similar suppressive effect of the heart rate, blood pressure and double product at rest and on exercise was seen after LA and Prop while the exercise capacity was increased. 3) The plasma level of propranolol was higher at 2 hours after Prop than LA administration, but there was no difference between LA and Prop at 4 and 24 hours after administration. 4) The plasma propranolol level at 4 hours after LA correlated with the percent reduction in exercise heart rate and with the percent reduction in the double product. Our study suggested that once-a-day administration of LA could improve patients' compliance and adds another choice to the list of clinically useful β-blockers for the treatment of angina pectoris on effort.

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Operative risk factors and postoperative late results were evaluated in 26 patients undergoing pulmonary artery reconstruction with a substitute valve. Seventeen extracardiac conduits bearing a valve were used in 16 patients and an in situ pulmonary valve insertion was carried out in the other 10. The surgical results were influenced by complexity of the underlying cardiac lesions and pulmonary vascular status, with a high mortality rate in patients with several cardiac defects including single ventricle, asplenia syndrome, complete atrioventricular canal etc. The mortality rate was 6% in patients with an immediate postrepair Ppv/sv of less than 0.75 and 77.8% in those with a Ppv/sv over 0.75. Postoperative Ppv/sv was mainly regulated by valve area index and a close correlation was obtained for the regression equation Ppv/sv = 0.41/(VAI)² + 0.36 (r=-0.61, p<0.05). To obtain excellent hemodynamics with a Ppv/sv of less than 0.50, valve area index should be over 1.7 cm²/M², and to eliminate re-implantation of the conduit after reaching adulthood, the diameter of the conduit should be 18 mm or more and the valve size 23 A, or more when a SJM valve is used.

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The postoperative changes of pulmonary vascular resistance (PVR) of two age groups of children with complete atrioventricular canal (CAVC) were compared. Patients were divided by age at the time of primary repair ; Group-1 (G-1, n=4) with age below 2 years (average 13.8 mo.) and Group-2 (G-2, n=5) with age over 2 years (average 44.0 mo.). All except one were Down's syndrome. Preoperatively, pulmonary to systemic resistance ratio (Rp/Rs) were 0.87±0.50 in G-1 and 0.41±0.13 in G-2 (n.s.), and postoperative study (average 6.5 mo.) showed no significant falls in Rp/Rs in both groups. However, G-2 showed significantly lower Rp/Rs postoperatively (0.79±0.19 in G-1 vs 0.27±0.12 in G-2, p<0.05). Mean pulmonary artery pressure (mPA) showed significant fall after surgery in only G-2 (66.8±6.6 to 31.8±11.6 mmHg, p<0.005). Anatomically, type-A showed better postoperative changes in mPA compared to type-C. This study summarized the early progression of pulmonary vascular obstructive disease with poor postoperative improvement even the primary repair was done before 2 years of age. The less advanced pulmonary vascular disease in G-2 might have some relations to the natural selection of the disease.

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The amount of phosphoric acid liberated from ATP by Ca²⁺ (Mg²⁺)-ATPase in microsomal fraction of guinea-pig thoracic aorta decreased with decreasing concentrations of calcium ions from 20.0 to 2.5 mM in the mixture of the enzyme and substrate. When CaCl₂ (2.5 mM) and MgCl₂ (5.0 mM) were present in the substrate, both nitroglycerin (0.1 to 1.0 mM) and SIN-1 A (a molsidomine derivative, 0.05 to 1.0 mM) increased the liberated phosphoric acid in a concentration-dependent manner. The contractile tension of smooth muscle prepared form guinea-pig thoracic aorta, which was previously increased by the pretreatment with prostaglandin F_2α (5.0 μM), was relaxed by both nitroglycerin and SIN-1 A (0.01 to 100 μM each) in a concentration-dependent manner. From the results, it is assumed that the stimulation of Ca²⁺ (Mg²⁺)-ATPase [Ca²⁺-pump ATPase] activity induced by nitroglycerin and SIN-1 A in the microsome of thoracic aorta takes part in the relaxation of contractile tension in the tissue.

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The hemodynamic changes of the left ventricle (LV) of golden hamsters surviving for 14 months after acute coxsackie B3 virus myocarditis were assessed with the use of a high fidelity micromanometer pressure system. Of 25 infected hamsters, 10 survived to the 14th month, and 4 of these had cardiomegaly. Body weight (BW) was 150.0±20.7 g (mean ±SD) (controls, 164.5±20.1 g, NS); heart weight (HW), 0.499±0.084 g (controls, 0.448±0.035 g, NS); and HW/BW, 3.39±0.79×10^-3 (controls, 2.74±0.23×10^-3, p<0.05). The hemodynamic data under anesthesia were: HR, 378±42 (controls, 414±43, NS); LVSP, 108±16 mmHg (controls, 126±16, NS); LVDP, 4.0±4.8 mmHg (controls, 0.6±0.7, NS); LVEDP, 9.7±7.5 mmHg (controls, 3.4±1.4, NS); peak positive dp/dt, 4690±1431 mmHg/sec (controls, 6714±1326, p<0.05); (dp/dt)/DP40, 56.8±9.8 sec^-1 (controls, 73.1±7.0, p<0.01); peak negative dp/dt, 3876±1072 mmHg/sec (controls, 4971±599, p<0.05); and time constant T of LV pressure fall, 7.7±1.3 msec (controls, 5.9±0.7, p<0.01). Five hamsters had congestion of the lungs and liver with or without an elevation of LVEDP. One of them had an organizing thrombus in the left atrium, and one had an aneurysm in the LV free wall. Though markedly varied in extent, residual myocardial fibrosis was always evident in the hearts in which isovolumic contractility and early diastolic relaxation of the LV were significantly impaired. In a clinical extension of these findings, it may be that some cases of dilated cardiomyopathy in man develop in a way similar to the pathological processes noted in this experiment.

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Clinical features and pathological findings were reviewed in 90 postmortem cases of valvular heart disease (VHD) to clarify the problems and limitations of medical management. The clinical features of severe mitral valve disease included congestive heart failure (CHF), with tricuspid regurgitation in many cases, atrial fibrillation, frequent ventricular premature beats, ventricular hypertrophy, cardiomegaly, increased pulmonary arterial pressure and abnormal hepatorenal function. The most common causes of aortic valve disease (AVD) were rheumatic fever and infective endocarditis, and the major causes of death were sudden death and intractable CHF. Autopsy in cases of AVD revealed marked left ventricular hypertrophy and dilatation, vegetations, thickening, adhesion and calcification in the aortic valve. Some patients died of cardiogenic shock due either to severely impaired cardiac function or to associated myocardial or pulmonary infarction. Abrupt onset of embolism was also related to death of the patients. The management of VHD must include the treatment of CHF and arrhythmias and the prevention of embolism. Appropriate timing for surgery and close follow-up by cardiologists is mandatory.

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Of the 652 cases with acquired valvular heart disease, 153 patients did not receive surgical therapies following cardiac catheterization studies. There were three types of reasons: mild symptoms, complications or high operative risks, and refusal. One hundred cases were not operated on immediately because of their mild symptoms, but 24 cases of them were aggravated during the follow-up periods and 15 underwent operations later. Twenty five cases were not operated on because of their complications or high operative risks. Eight of them died, 5 cardiac and 3 non-cardiac deaths. One was operated on later and another was aggravated with congestive heart failure. Twenty eight were refusal cases. Two of them died, 6 were aggravated and 7 were operated on later with one operative death. In this paper, several criteria were proposed for indications of surgery for the mild cases, and the limitations of the surgical therapies in the severe or complicated cases and the management of the refusal cases were discussed.

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One of the major causes of postoperative morbidity and mortality after valve replacement surgery is the prosthetic valve substitute itself. In this discussion, therefore, we make a fundamental evaluation of hydrodynamic valve function and present our clinical results following valve replacement with the Bjork-Shiley valve prosthesis, the Hancock porcine xenograft and the Ionescu-Shiley bovine pericardial xenograft. In an experimental study using a mechanical simulator system, the pericardial xenograft displayed superior hydrodynamic characteristics compared to other two valve subdtitutes. Postoperative hemodynamic evaluation further indicated that the pericardial xenograft performed significantly better than the porcine xenograft regarding transvalvular pressure gradient, effective valve area and cusp opening. In addition, data from 387 patients with aortic, mitral or both types of valve replacement who had received one of the three kinds of valve substitute were analyzed. Systemic thromboembolic complications occurred in one patient with an aortic Bjork-Shiley valve (0.6% per patient-year), six with mitral Hancock xenografts (2.2% per patient-year) and one with an aortic and mitral Hancock xenograft (2.2% per patient-year). The incidence of prosthetic valve endocarditis was 0.84% per patient-year for the Hancock xenograft and 1.84% per patient-year for the Ionescu-Shiley xenograft. It was concluded that the hemodynamic and antithrombogenic advantages of the pericardial xenograft proven by our mid-term follow-up study make it the valve substitute of choice. However, careful attention is required regarding prosthetic valve endocarditis tissue heart valves, which are more susceptible to infection than mechanical ones, and the long-term durability of the pericardial xenograft remains to be confirmed.

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The pathophysiology of advanced valvular heart disease and its clinical implications were analyzed. The study was undertaken primarily on 153 recent patients with implantation of central flow valves. The operative mortality rate was 3.9%, with deaths except one related to LOS. There was a higher incidence of LOS in left ventricular volume-overloaded hearts, and a much higher incidence in patients associated with TR : 70% of TR cases with RVEDP higher than 15 mmHg developed LOS. Cardiac contractile reserve proved to be useful index for predicting immediate postoperative and long-term results; less favorable results were indicated in patients with PWE below 10 mm even after epinephrine infusion. In volume-overloaded hearts, the muscle cell diameter of the left ventricle increased proportionally to the dimension of the left ventricle, with interstitial fibrosis representing irreversible morphological change. Patients with a prolonged indocyanine green disappearance rate showed fibrosis of the liver and were complicated more frequently by LOS, hepatic and renal disturbance and increased mortality. Patients with cardiac cachexia were liable to develop LOS postoperatively, and preoperative GIK therapy appeared to be effective in improving depressed metabolism and hemodynamics, except in patients with severe TR.

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The purpose of this study was to clarify the characteristic features of aortic valvular heart disease (VHD) compared with mitral VHD and to discuss the optimal time for replacement surgery. Serial echocardiographic studies on a medically treated group with aortic regurgitation disclosed that those patients presenting with congestive heart failure or dying during follow-up period showed the systolic dimension of the left ventricle (LVDs) over 55 mm and percentage fractional shortening (%FS) to be less than 27%. Factors influencing the result of replacement surgery for aortic regurgitation was studied by comparing the group in which the postoperative course was uneventful with the group in which postoperative support with catecholamine or the intra-aortic balloon pumping (IABP) was necessary. Systolic dimension of the left ventricle, %FS and mVcf by echocardiography were significantly different in the two groups. It is concluded from these results that aortic valve replacement for the aortic regurgitation should be performed just before, or immediately after, LVDs exceeds 50 mm, %FS falls below 28% and mVcf falls below 0.9, even in asymptomatic patients.

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We have studied the long-term results of valve replacement operations in 591 patients, one year or more after surgery, and also analyzed rates of social return in 523 patients (response rate, 86.1 per cent) by questionnaire. Of the 591 patients, 81 patients suffered early death (mortality rate, 13.7 per cent) and 41 patients late death (mortality rate, 6.9 per cent). The causes of the latter were left atrial thrombus (18 cases), heart failure (10 cases), artificial valve failure (five cases), renal failure (two cases) and hepatic insufficiency, infection and accident (one case each). Second replacement was performed in 18 patients (3.0 per cent), 49 months on average from the first operation. The survival rate at the 12th postoperative year was 68.7 per cent. The overall rate of social return after valve replacement was 64.8 per cent, including 74.8 per cent for mitral valve replacement, 54.3 per cent for aortic and 51.5 for multivalvular. The rate of social return has been improved to 76.4 per cent in the last five years.

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We re-evaluated the indications for mitral valve replacement and reconstruction, and attempted to determine the optimal time for aortic valve replacement. (1) The actuarial event-free survival rate in patients undergoing open mitral commissurotomy for mitral stenosis with far-advanced subvalvular deformities was 78 per cent at 11 years after surgery and similar in patients undergoing mitral valve replacement for mitral stenosis. Postoperative clinical improvements compared favorably with those in patients undergoing mitral valve replacement. If quality of postoperative life in patients not requiring anticoagulants is borne in mind, open mitral commissurotomy should be given strong consideration as the procedure of choice for the majority of patients with mitral stenosis. (2) The long-term results of reconstructive procedures for mitral regurgitation largely depend upon the pathological anatomies contributing to the development of mitral regurgitation. The results were less satisfactory in patients with fibrotic changes of valvular and subvalvular tissue than in patients undergoing mitral valve replacement for mitral regurgitation. (3) In aortic valve replacement, the postoperative prognosis was poor in patients with a preoperative left ventricular end-systolic volume index exceeding 200 ml/m² and left ventricular ejection fraction less than 0.35. Operative management of patients with aortic valve disease should be considered, before severe left ventricular systolic dysfunction is evident.

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We examined the application and timing of valve replacement in 105 cases of aortic regurgitation, from the aspect of etiology, clinical findings and prognosis. The mortality for patients after aortic valve replacement was 12.9%. This was lower than that for the patients not operated up on, which was 35.0%. The mortality after valve replacement for patients having acute aortic regurgitation due to active endocarditis was as high as 80%, which showed the limitations of medical and surgical therapy. In cases of chronic aortic regurgitation, if valve replacement is performed within 3 years of the appearance of heart failure symptoms, the mortality is 0. Even after three years, valve replacement is applicable if there are no ventricular premature contractions. CTR 65%, %FS 21%, R/Th 2.9 and EF 38% were considered to be the critical factors for postoperative prognosis.

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Antithrombic medication is effective in the prevention of thromboembolic complications after valve replacement. Therapy with oral anticoagulant (warfarin), platelet inhibitor drugs and long-term warfarin administration an have good clinical results. However, thrombosis may occur in the early postoperative period, when the oral administration of warfarin is impossible. We have evaluated treatment with urokinase, low-dose heparin and dipyridamole, administered intravenously, instead of warfarin, during the early postoperative period. This procedure was carried out in 30 patients, among whom there was no evidence of thrombosis or of such side-effects as bleeding or a marked tendency to bleed.

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