This study was performed to determine the effect of recombinant human erythropoietin (rEPO) on preoperative autologous blood donation in patients undergoing elective coronary bypass or valvular operations. Nineteen patients received 200 u/kg of rEPO intravenously 3 times a week, and 210 mg/day of iron sulfate orally, for 2 weeks before surgery (EPO group). Seven matched patients only took the same dose of iron sulfate (control group). Bone marrow was aspirated from the sternum during surgery, and the Myeloids/Erythroids ratio was calculated in 13 patients of the EPO group. The total donated blood mass was 853±231 g in the EPO group, and 657±140 g in the control group (p<0.05). The average increase in hemoglobin (Hb) mass from admission to the day before surgery was 87±33 g in the EPO group, and 24±13 g in the control group (p<0.001). Furthermore, the logarithm of the ratio of "increased Hb mass / Hb mass at admission" was significantly correlated to the Myeloids / Erythroids ratio (r= -0.9130, p<0.01). These results strongly indicate that rEPO is a very useful agent for predonation of autologous blood for cardiac operations.

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To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72±0.05; CAD, 0.86±0.13; p<0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2±8.9 mmHg) than in the control group (11.5±4.0 mmHg)(p<0.01). PAWP at peak exercise was &gne; 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r=0.67, p<0.01) in the CAD group, but not in the control group. An SBP ratio of &gne; 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of &gne; 20 mmHg in CAD patients. After the administration of a calcium channel blocker, the SBP ratio showed a sensitivity of 80% and a specificity of 95% in the CAD group (n=25), and was significantly correlated with the PAWP at peak exercise (n=25, r=0.69, p<0.01). These observations indicate that the SBP ratio is a good indicator of exercise-induced impairment of left ventricular filling dynamics during supine leg exercise.

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To investigate the clinical significance of carbohydrate antigen 125 (CA125), an antigen related to ovarian cancer, in patients with pericardial effusion, we examined the relationship between serum levels of CA125 and the presence or severity of pericardial effusion. Fifty-seven patients (25 with heart failure. 22 with pericardial metastasis, 4 with hypothyroidism, 4 with renal failure, and 2 with other diseases) in whom pericardial effusion was confirmed by echocardiography or autopsy, were used as subjects. Thirty-seven of these patients (65%) tested positive for CA125 in the serum. Of these, no significant differences in serum levels of CA125 were found between patients with benign and those with malignant underlying diseases or between those with, or without, pericarditis. However, CA125 values were higher in the patients with larger pericardial effusions and the serum level decreased when the pericardial effusion reduced. In some cases, the serum level normalized before the effusion resolved. Pericardial drainage was performed on 6 patients with cardiac tamponade. Four of these 6 patients had high serum CA125 levels and recurrent pericardial effusion. The other 2 patients had normal serum CA125 levels and no recurrence of effusion. An immunohistological study showed that a positive stain of pericardial tissues reacting to CA125 antibodies correlated to higher serum and pericardial fluid levels of CA125 than the levels of groups staining negative to the antibody. These results suggest that CA125 can be useful in assessing the status and clinical course of this disease.

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To investigate the effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in QRS amplitude, we reviewed treadmill exercise electrocardiograms. In 10 normal young men, R_v5 amplitude decreased and S_v1 amplitude increased at peak exercise, and returned to the resting value in the recovery period. In 10 patients with aortic regurgitation, R_v5 and S_v1 amplitudes increased after 5 min of recovery. In 12 patients with essential hypertension and 10 with idiopathic hypertrophic non-obstructive cardiomyopathy, R_&amp;l;tv5> amplitude remained unchanged or higher at peak exercise compared with the resting value, but patterns of serial changes were similar to that of normal subjects. In 9 patients with atrial septal defect. R'_v1 amplitude increased with exercise, whereas it remained unchanged in 12 with isolated complete right bundle branch block. In 5 patients with mitral stenosis, S_v1 amplitude decreased at peak exercise. In conclusion, changes in QRS amplitude with exercise are influenced by hemodynamic abnormality and myocardial hypertrophy, and a major determinant of these serial changes seems to be the change in ventricular volume.

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We analyzed 24 h ECG recordings of 29 patients with frequent (>2000/day) ventricular premature contractions (VPCs) to evaluate: 1) the relationship between VPC frequency and heart rate (HR); 2) the relationship between the coupling interval (CI) of VPCs and HR; 3) the time course of changes in VPC frequency following an abrupt and sustained increase in HR; and 4) the effect of oral diltiazem (90 or 180 mg/day for 4 weeks) on VPCs. Based on the patterns of relationship between VPC frequency and HR, patients were divided into 2 groups: 1) 17 patients with a positive correlation, the P group (a linear increase in VPCs with increasing HRs); and 2) 12 patients with a non-positive correlation, the NP group. The NP group showed either a linear decrease in VPCs with increased HRS (4 patients) or an increase in VPCs at low HRS and a decrease at high HRS (8 patients). In all cases, an increased HR was associated with a shortening of CI. In the P group, changes in VPCs after an abrupt in-crease in HR showed 2 types: 1) delayed-ascent type, in which VPCs increased as the duration of HR increase was prolonged (cumulative effects of heart beat) (7 patients); and non-delayed-ascent type (10 patients). Diltiazem reduced VPCs≥75% in all of the 7 delayed-ascent-type patients, compared with 3 of the 10 non-delayed-ascent-type patients (p<0.05) and none of the 12 patients in the NP group (p<0.001). The VPCs of delayed-ascent type had several important features characteristic of delayed afterdepolarizations induced in animal experiments, suggesting that these VPCs may be due to delayed afterdepolarizations.

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Right and left ventricular function in acute myocardial infarction (AMI) was assessed by ECG-gated magnetic resonance imagine (MRI) in 64 patients and 8 volunteers. Five short axis images for intrinsic cardiac long-axis of the left ventricle were obtained at 9 msec and 309 msec after the R wave as end-diastole and end-systole. Right and left ventricular volumes were measured by Simpson's rule. The intraobserver variabilities in right and left ventricular ejection fraction (RVEF: r=0.94, LVEF: 0.89) were excellent. The interobserver variabilities in RVEF (r=0.61) and LVEF (r=0.77) were fair. LVEF, but not RVEF, was significantly reduced in patients with AMI. Among left ventricular dysfunction (LVEF≤40%) patients, 50% exhibited right ventricular dysfunction (RVEF≤40%). Among patients without left ventricular dysfunction, only 12% exhibited right ventricular dysfunction. In left ventricular and biventricular dysfunction compared with control, the left ventricular end-diastolic volume index increased (65±10 ml/m², 68±12 ml/m² vs 54±8 ml/m²), the end-systolic volume index increased (40±16 ml/m2, 43±7 ml/m2 vs 18±1 ml/m²), and the right ventricular end-diastolic volume index decreased (52±13 ml/m², 53±20 ml/m² vs 65±8 ml/m²). MRI can thus be used to assess ventricular systolic function. Since patients with left ventricular dysfunction revealed a high incidence of right ventricular dysfunction, an interaction between the left and right ventricles may occur in ventricular dysfunction.

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The relationships between pressure rate product (PRP) and flux (PCr→ATP) or flux (Pi→ATP) were studied in isolated perfused rat hearts by the saturation transfer method using ³¹P-NMR. The effects of propranolol and diltiazem on phosphate metabolism were also studied. After a 40 min preischemic period, the hearts were subjected to a 15 min period of ischemia, followed by 60 min of reperfusion. Propranolol (0.4-1.2μM) or diltiazem (3.0-6.0μM) was infused for 30 min before ischemia and reinfused after reperfusion for 60 min. The flux (PCr→ATP)/PRP ratio at reperfusion did not differ from that at preischemia. This value was also not affected by propranolol or diltiazem treatment. However, the flux (Pi→ATP)/PRP ratio at reperfusion was significantly less than that at preischemia. Moreover, this value was significantly improved by propranolol or diltiazem treatment. This study demonstrates that 1) flux (PCr→ATP) has a good correlation with cardiac performance, 2) stunned myocardium needs less ATP turnover for survival of its depressed contractile activity, and 3) flux (Pi→ATP) can limit recovery of postischemic performance. Protective effects of propranolol and diltiazem are exerted on the flux (Pi-ATP), i.e. ATP derived from glycolytic flux, in the reperfused heart.

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There are few reports on the relationship between right ventricular performance and its myocardial oxygen consumption (RVMVO₂). The present study was conducted to investigate the relationship between RVMVO₂ and the mechanical performance of normal and hypertrophic right ventricles in open-chest dogs. Right ventricular hypertrophy (RVH) was induced by producing chronic right ventricular pressure overload by banding the pulmonary arteries of 8 puppies for 6 months. The experiment was performed under basal conditions and after increasing the RVMVO₂ in the eight dogs with RVH as well as in 20 normal dogs. The RVMVO₂ showed significant positive relationships with right coronary (RCA) flow, right ventricular systolic pressure, and right ventricular pressurerate product (PRP) in both the normal right ventricle and RVH hearts. However, the slope between the PRP and RVMVO₂ was significantly steeper in the normal right ventricle (RV) than in the hypertrophic RV. When the PRP was normalized for the thickness of the right ventricular free wall, the slope of the two regression lines merged into a single line of fit. These results suggest that the pressure-rate product can be used to predict myocardial oxygen demand not only in the normal RV but also in well-compensated, hypertrophic RV. Isoproterenol induced smaller increases in cardiac output in the dogs with RVH than in those with normal RV. It also appears that the cardiac output of the hypertrophic RV is less sensitive to β-adrenoceptor stimulation than that of the normal RV.

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The relationship between early afterdepolarization (EAD) and the occurrence of torsades de pointes (TdP) was studied in a canine model. Twelve dogs of both sexes, weighing 9.9-16 Kg, were studied. After reducing the concentration of serum potassium to 3.0-4.0 mEq/l, by adrninistration of calcium polystyrene sulfonate at 15-20 g/day for 1 or 2 weeks, a 6F electrode catheter was introduced via the femoral vein and positioned at the atrioventricular (AV) junction. Complete AV block was produced by catheter ablation using a high frequency current. A Franz 6F catheter was introduced into the right ventricle to record monophasic action potentials (MAPs) using the contact electrode technique. After a stable recording of the MAPS Was achieved. cesium chloride (CsCl; 1 mM/Kg) was administered as an intravenous bolus over 15 sec. The MAPS and electrocardiogram (ECG) changes were simultaneously recorded for 30 min after the administration of CsCl. The administration was repeated several times at intervals 30 min. Sustained or non-sustained ventricular tachycardia was produced in all dogs. EAD appeared in 8 of 12 dogs. When EAD developed sufficiently high amplitude, ventricular premature beats occurred near the peak of EAD and TdP was induced in 3 of 8 EAD-positive dogs. TdP was not induced in EAD-negative dogs. Although TdP was comparatively difficult to induce. EAD-triggered activity was suggested to be one of the necessary conditions for TdP, because TdP occurred only when EAD reached a sufficiently high amplitude to produce ventricular premature beats.

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The lability of an intracoronary thrombus, which is common in the case of unstable angina. indicates the presence of endogenous fibrinolysis. To prove our hypothesis that suppression of coagulation facilitates the thrombolytic process, 10w molecular weight heparin (LMWH) was given intravenously to dogs with intracoronary thrombi induced by copper coils. LMWH caused reperfusion in this model and suppressed the formation of intracoronary thrombi, thus sup-porting our hypothesis.

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We discuss here the effect of the addition of trinitroglycerin to the cardioplegic solution on the isolated rat heart after eight hours of storage. This effect was evaluated by measuring cardiac function as well as myocardial calcium and enzymes. Male Wistar rats were divided into three groups based on the concentration of trinitroglycerine in the cardioplegic solution. In the control group, the fluid used was a crystalloid cardioplegic solution (K⁺ 25 mEq/L) without trinitroglycerin and for groups I and II, trinitroglycerin was added at concentrations of 2 μg/ml and 5 μg/ml, respectively. All hearts were arrested with the cardioplegic solution at 4°C and then immersed for eight hours in Euro-Collins' solution at 4°C. The postperfusion coronary flow showed higher rates for groups I and II than for the control group (p<0.05), while the difference between groups I and II was not significant. In group I, the total concentrations of creatine kinase-MB, lactate and malondialdehyde after reperfusion showed the lowest levels; this group also had the lowest content of myocardial calcium. These results indicate that the addition of nitroglycerin, especially at a concentration of 2 μg/ml, to the cardioplegic solution elicits better cardiac function for immersed rat heart.

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Atherosclerotic lesions usually occur in the proximal and middle portion of the coronary arteries. Multiple obstructive lesions appearing only in the peripheral branches without lesions in the proximal or distal portion have not been re-ported. We encountered a patient with ischemic heart disease showing multiple obstruction in the peripheral branches of the right and left coronary arteries without significant stenotic lesions in the proximal or middle portion. This 49-year-old male was admitted to Yamada Red Cross Hospital due to angina pectoris. Coronary risk factors for him included hypertension, abnormal glucose tolerance, smoking habit, and obesity. Laboratory studies showed a complete blood count and normal blood chemistries, as well as thromboplastin and prothrombin times. Coronary angiography showed multiple obstruction or marked stenosis in the distal portion and peripheral branches; there was no stenosis in the proximal and middle portions. Left ventriculography showed severe hypokinesis in the diaphragmatic segment. Biopsy of the left ventricular endocardium showed interstitial fibrosis but showed no abnormalities in the myocardial fibers or cell infiltration to perivascular areas and vascular walls. Coronary angiography after two months showed multiple lesions, as previously observed. Although ischemic heart disease is caused by various types of vasculitis, embolism, coronary spasm, and fibromuscular dysplasia, in this patient, there were no findings suggestive of causes other than atherosclerosis. This case is interesting in terms of rare angiographic findings and its cause.

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A 26-year-old man was admitted with a high fever, oliguria, skeletal muscle weakness, and cardiogenic shock which led to a diagnosis of acute myocarditis and acute rhabdomyolysis. During treatment with hemodialysis and calcium supplementation, because of severe hypocalcemia, a massive calcification of both right and left ventricular myocardium gradually became apparent with repeated computed tomographic (CT) examinations. Technetium-99m scannings more clearly delineated the markedly accumulated calcium in the myocardium, while significant activity was not detected in other soft tissues. Histopathological examinations by myocardial biopsy revealed a large amount of fibrosis and calcium deposits, and serial CT scans showed a gradual regression of the calcium deposition, suggesting that this rare form of massive dystrophic calcification may parallel changes in the severity of myocarditis, and may be associated with abnormalities in calcium metabolism secondary to rhabdomyolysis-induced acute renal failure.

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We report an extremely rare case of dilated cardiomyopathy manifested by exercise-induced left bundle branch block. A 63-year-old female came to our hospital because supraventricular arrhythmia had been detected at a check-up. A treatmill exercise test induced left bundle branch block. However, chest X-ray and echocardiography revealed no abnormal finding. Two years later, the patient experienced exertional dyspnea. A chest X-ray examination showed cardiomegaly, and echocardiography showed a moderate impairment of left ventricular function with left ventricular dilatation. The diagnosis of dilated cardiomyopathy was made by left ventricular myocardial biopsy. No previous cases have initially shown exercise-induced left bundle branch block which was followed by left ventricular dysfunction due to dilated cardiomyopathy. Careful long-term observation of the clinical course is necessary in patients with exercise-induced left bundle branch block which shows no significant underlying disease.

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