To determine the clinical significance of reverse redistribution (RR), resting thallium-201 myocardial single-photon emission computed tomography was per-formed once or twice in 80 patients in subacute phase (1 week to 2 months) of myocardial infarction. Thirty eight patients demonstrated RR on at least one study (group RR) and 32 a fixed defect only (group FD). Group RR had significantly smaller defects than group FD. Standardizing the relation of the severity of wall motion abnormality of left ventricle on echocardiogram with that of perfusion defect, in group RR wall motion abnormality in the acute and subacute phase reflected the defect of delayed image, while that in chronic phase, which was thought to reflect the viability of myocardium in the infarct region, reflected the defect of initial image. In serial thallium-201 studies, only the defect of delayed image of group RR improved on the second study, while the defect of initial image of group RR and defect of group FD did not improve. Wall motion of group RR improved with the disappearance of RR, and when RR remained, wall motion did not improve so much. We concluded that RR was thought to be demonstrated in viable myocardium with severe wall motion abnormality.

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In order to elucidate the mechanisms of the appearance of hemodynamic right ventricular infarction (RVI), we studied right and left ventriculograms and hemodynamic findings in 52 patients with acute inferior myocardial infarction. Right ventricular wall motion disturbance (RVWMD) was detected in 69% of patient but hemodynamic RVI was observed only in 16%. Among patients with RVWMD, there was no significant difference in right ventricular ejection fraction between those with (group III) and without (group II) hemodynamic RVI, suggesting that right ventricular (RV) systolic dysfunction does not independently produce hemodynamic RVI. Right ventricular end-diastolic volume index was similar in groups II and III in spite of higher mRA in group III. The result suggested that the RV compliance of group III was decreased. Heart rate (HR) was significantly lower in group III than in group II. Not only physiologic pacing but also VVI pacing significantly improved hemodynamics in patients with hemodynamic RVI. A positive correlation between HR and cardiac index was observed (r=0.56, p<0.001) in patients with RVWMD. Decreased RV compliance and bradycardia were considered to be determinants of the appearance of hemodynamic RVI. Volume loading did not improve hemodynamics significantly in patients with hemodynamic RVI.

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In order to investigate the relationship between sympathetic activity and postexercise systolic blood pressure (SBP) and exercise-induced ventricular arrhythmias in patients with coronary artery disease (CAD), we studied 38 patients and 9 normal subjects who underwent treadmill testing. Peak pressure-rate product was similar in the 2 groups. The plasma concentrations of norepinephrine and epinephrine at rest and immediately after exercise were significantly higher in patients with CAD compared with normal subjects (norepinephrine at rest, p<0.01; norepinephrine immediately after exercise, p<0.05; epinephrine at rest, p<0.05; epinephrine immediately after exercise, p<0.05). The level of norepinephrine immediately after exercise was significantly higher in 15 patients with a postexercise SBP increase than in 23 patients without that SBP change (p<0.05), whereas the level of epinephrine was similar in the 2 groups. The level of epinephrine immediately after exercise was significantly higher in 10 patients with exercise-induced premature ventricular contractions than in 28 patients without those arrhythmias (p<0.05), whereas the level of norepinephrine was similar in the 2 groups. We conclude that a postexercise SBP increase is related to the augmentation of sympathoneural activity and that exercise-induced ventricular arrhythmias are related to the augmentation of sympathoadrenal activity.

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We compared survival patterns in 61 medically treated and 78 surgically treated patients at a Japanese community hospital. The 2 groups were matched for presence of significant 3 vessel disease, resting ejection fraction of more than 40%, a bypassable left anterior descending artery, sex, and age. All surgical patients received saphenous vein grafts. The patients treated surgically had better 5 and 9 years survival rates than the medically treated patients (93% and 85% vs 74% and 55%, respectively; p<0.01 by Cox-Mantel analysis). Five and 9 years rates of absence of ischemic events (non-fatal myocardial infarction and primary cardiac death) were also better in the surgical group than the medical group (92% and 87% vs 66% and 52%, respectively; p<0.001). Of the surgically treated patients, 5 died perioperatively, 3 had late cardiac deaths and 2 had a nonfatal infarction. Among the medically treated patients, 16 had cardiac deaths, and 6 had non-fatal infarctions. Although our study was non-randomized, we have shown an advantage for surgical treatment of patients with 3-vessel coronary disease.

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It is well known that isoproterenol (ISO) a nonselective β adrenoceptor agonist induces cardiac hypertrophy. It can be assumed that, in addition to its direct cardiac effect, ISO has a cardiac trophic effect via stimulation of the renin angiotensin system. Synthesis of polyamines is facilitated in cardiac hypertrophy and polyamine levels are rapidly elevated prior to an increase in heart weight. In the present study, we investigated whether captopril (30 mg/kg body weight, daily) could attenuate cardiac hypertrophy and elevation of cardiac polyamine levels in rats, which effects were elicited by a chronic (1- or 2-weeks) and repeated administration of a small dose (0.5 mg/kg body weight) of ISO. Cardiac hypertrophy was assessed by an increase in the wet weight and RNA content of the heart. Polyamines were analyzed by HPLC. Captopril alone did not affect either heart weight/body weight ratio or cardiac contents of polyamines and nucleic acids at the end of the second week. In isoproterenoltreated rats, the above parameters, except for putrescine content on day 14, were significantly increased on both day 7 and day 14. Captopril slightly attenuated ISO-induced cardiac hypertrophy and significantly prevented the ISO-evoked increase in the contents of RNA, spermidine, and spermine at the end of the second week. These results suggest that the ISO-evoked increase in cardiac polyamines was mediated, at least in part, by the renin angiotensin system, which was stimulated by ISO.

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The purpose of this study was to investigate the therapeutic effect of an α₁-blocker, bunazosin, using an experimental murine model of congestive heart failure induced by viral myocarditis. This model is characterized by a high incidence of severe myocarditis and subsequent congestive heart failure, and is suitable for the evaluation of the effect of drugs. To estimate myocardial damage objectively and quantitatively, we used antimyosin monoclonal antibody in addition to histopathological grading. Four-week-old BALB/C mice were inoculated with encephalomyocarditis virus. The mice were injected daily with bunazosin or saline as a placebo from the day of viral inoculation until day 7 (protocol-1) or day 14 (protocol-II), or from day 4 to day 14 (protocol-III). They were then injected with 1.5 μCi of indium-111 Iabeled antimyosin anti-body and were killed 24 h later. The antimyosin cardiac uptake was counted and histopathological grading was performed. The heart-weight to body-weight ratio, left ventricular dimension, histopathological grades and antimyosin cardiac uptake were significantly lower in the bunazosin group than in the placebo group in protocol-II, but not in protocol-1 or protocol-III. Bunazosin showed a protective effect against viral myocarditis only when it was started early after infection and continued until the stage of congestive heart failure.

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We studied 141 patients to evaluate the pathogenesis and clinical picture of high-risk unstable angina (UA), designated as impending myocardial infarction (IMI) in this study, or severe early post-infarction angina (PIA). IMI and PIA were diagnosed when chest pain appeared at rest and lasted 15 min or more de-spite extensive pharmacological therapy during hospital stay among consecutive 510 patients with UA. All patients underwent coronary angiography urgently within 72 h after chest pain, and were divided into 2 subgroups according to ST segment shifts during chest pain. In IMI, 42 patients with ST depression had higher incidences of prior myocardial infarction (MI), worsening UA, mul-tivessel disease and complex lesions such as eccentric irregular lesion or ulceration. On the contrary, in 44 with ST elevation, new onset UA, single vessel disease and coronary thrombus (CT) were dominant. In PIA, 32 patients with ST elevation revealed higher incidences in Q wave MI, ST elevation at the MI onset, single vessel disease and CT, compared to 23 with ST depression who showed a high proportion of complex lesions. Thus, it was evident that there was a common link between the pathogenesis of IMI and PIA. The therapeutic options were also different in the groups according to ST segment shift. We conclude that ST segment shifts during chest pain may be useful for determining the pathogenesis and clinical features of high-risk UA.

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To clarify the pathogenesis of an impending infarction and to investigate the difference between the pathogenesis of an acute myocardial infarction and an impending infarction, we have performed percutaneous transluminal coronary angioscopy in 13 patients with an impending infarction and in 13 patients with an acute myocardial infarction. As a result, coronary thrombi were observed in 12 of the 13 patients with an impending infarction, and a similar frequency of thrombi was observed in the patients with an acute myocardial infarction. Further, grayish white thrombi were observed in 9 of 12 patients with an impending infarction, but no such thrombi were noted in those with an acute myocardial infarction. Reddish thrombi, however, were observed in all patients with acute myocardial infarction, whereas such thrombi were observed in only 3 of 12 patients with an impending infarction. Informatively, occlusive thrombi occurred more frequently in patients with an acute myocardial infarction than in those with an impending infarction. As a thrombus plays an important role in an impending infarction, we also evaluated the effect of anticoagulant and thrombolytic therapy for an impending infarction in 79 patients. The incidence of recurrent angina and a subsequent acute myocardial infarction were significantly higher in non-heparin-treated patients and in thrombolytic-treated patients than in heparin-treated patients. In conclusion, a thrombus plays an important role in the pathogenesis of an impending infarction and in an acute myocardial infarction, though the characteristics of the thrombus differ in each instance. This difference may account for the differing results of thrombolytic therapy. Heparin was found an effective treatment for myocardial ischemia in an impending infarction.

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Among 366 unstable angina pectoris patients at our hospital, myocardial infarction was common (15.7%) in those with attacks of chest pain lasting for at least 20 min. There was also a high incidence (30.3%) when chest pain continued after the start of inpatient treatment. To investigate the etiology of unstable angina, coronary arteriography was performed in both the unstable and stable stages in these patients and the results were compared. The role of coronary spasm and coronary thrombosis in unstable angina was investigated, and the efficacy of continuous infusion of either diltiazem or isosorbide dinitrate as treatment for these patients was compared. Coronary arteriography in the unstable stage showed, no clear differences in the morphology of the stenotic site and the degree of stenosis between the patients with and without infarcts when urokinase or isosorbide dinitrate were injected into the coronary arteries. When drug treatment was effective, the angina was stabilized without any improvement in the degree of stenosis or the morphology of the involved coronary vessel. Thus, it was difficult to predict the response to treatment from coronary arteriography performed in the unstable stage. Diltiazem was more effective than isosorbide dinitrate, and it appears that some action other than coronary dilatation was involved in achieving the remission of unstable angina.

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The influence of coronary angiographic findings and treatment on clinical out-come was determined in 104 patients with impending myocardial infarction (unstable angina with prolonged chest pain and persistent electrocardiographic changes on admission). Coronary arteriography was performed on day one (aggressive strategy) in 50 patients and following medical treatment (conservative strategy) in 48 patients, of whom 40 were unstable. Six elderly patients were treated medically without angiography. A complex eccentric morphology of the coronary vessels was the most common finding in both groups, but the incidence of intracoronary thrombus was significantly higher in the aggressive strategy group (78%) and in unstable patients (77%) compared with patients controlled medically (24%). Severe multivessel disease was also common in refractory patients without thrombus. Percutaneous transluminal coronary angioplasty was less successful and produced more distal emboli in patients with thrombus. Emergency intervention was applied to 90% of the aggressive strategy group-it failed to improve the in-hospital outcome, but shortened hospitalization significantly. Elderly patients treated medically without angiography had the highest mortality. We concluded that intracoronary thrombus plays a major role in the pathogenesis of impending infarction, and that the majority of such patients cannot be stabilized medically. An aggressive strategy can be applied safely to impending infarction and will shorten hospitalization.

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Percutaneous transluminal coronary angioplasty (PTCA) was successful in 91% of 76 patients with unstable angina pectoris refractory to pharmacological treatment. However, the rate of acute occlusion and reocclusion was rather high (95). Restenosis developed in 56.5% of successful cases after initial PTCA, and 29 patients underwent 2nd, and nine 3rd PTCA. Most refractory unstable angina can be controlled by PTCA, which may require repeating in some patients.

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Intracoronary thrombodynamics in acute coronary syndromes was studied with an experimental canine model. An intracoronary thrombus was precipitated at the mock ruptured atheromatous plaque consisting of cholesterol and collagen. In 8 of 10 control models, acute myocardial infarction (AMI) was induced by intracoronary occlusive thrombus I h after the start of the experiment. Coronary blood flow decreased continuously (Type A, n=5) or cyclically (Type B, n=3) to end in AMI. Effects of pharmacological interventions to prevent AMI were also studied with the model. An intravenous bolus injection of a thromboxane synthetase inhibitor (RS-5186), heparin, a thrombin inhibitor (argatroban), and a thrombolytic agent (urokinase) was performed in 10 models for each drug. The incidence of AMI was significantly decreased to 3 of the 10 models injected with the thromboxane synthetase inhibitor and heparin (p< .05, each drug group vs. control). The preventive effect of argatroban was more potent and AMI occur-red in 2 of 10 models (p<0.01, argatroban vs control).

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We examined the hypothesis that combined actions of anticoagulant (heparin) and Y-20811, thromboxane A₂ Synthetase inhibitor (TXSI), or S-1452, receptor blockade (TXRB), can provide better antithrombotic protection than TXSI or TXRB alone. In 20 of 33 dogs instrumented, placement of a critical stenosis at a focus of coronary vascular injury initiated a reproducible cyclic coronary flow reduction (CCFR) . TXSI (1 mg/kg, IV) perfectly inhibited CCFR in 6 of 10 dogs (60%), and was associated with a significant decrease in 11-dehydro-TXB₂ (85±8% of control; p<0.05) and an increase in 6-keto-PGF_1α (155±38%; p<0.05) in coronary sinus blood samples. In the remaining 4 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. On the other hand, TXRB (1 mg/kg, IV) perfectly inhibited CCFR in 7 of 10 dogs (70%), and was accompanied by a significant increase in 6-keto-PGF_1α (214±65%; p<0.05) and unchanged TXB₂ level. In the remaining 3 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. Thus, the combination of anticoagulant and TXSI or TXRB were more effective than TXSI or TXRB alone in abolishing thrombotic CCFR, suggesting that the combination might be effective for treating patients with impending myocardial infarction.

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