Several studies have demonstrated an increased level of plasma plasminogen activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD). However, the concentration of PAI-1 in platelets, which accounts for more than 90% of the blood PAI-1, is unknown in these patients. The present study evaluated the concentrations of PAI-1 and several fibrinolytic factors in the plasma and platelets of patients with CAD and the serial changes in patients with acute myocardial infarction (AMI). All 72 subjects had coronary angiography and were divided into 3 groups: CAD(-) group without coronary artery stenosis or myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the AMI group admitted within 24h of symptom onset who underwent successful percutaneous transluminal coronary angioplasty (n=22). The concentrations of plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA·PAI-1 complex were similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI group compared with the 2 CAD groups. There were no significant differences between the 3 groups in the plasma concentrations of thrombin·antithrombin III complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), β-thromboglobulin (β-TG), and platelet factor 4 (PF-4). The platelet PAI-1 concentrations did not differ between the CAD(-) and CAD(+) groups, but was greater on day 1 in the AMI group compared to the CAD groups. The platelet β-TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1 rapidly decreased by day 5 and remained low on day 28 compared with day 1. The platelet PAI-1 concentration gradually decreased by day 5 and was further decreased by day 28. The serial changes of the plasma t-PA and t-PA·PAI-1 complex during the course of AMI were similar to those of the plasma PAI-1. A positive correlation was found between the plasma and platelet PAI-1 in all 72 patients, but not in the AMI group alone. These results suggest that the PAI-1 that has accumulated in platelets at the onset of AMI might be released in large amounts into the plasma, resulting in an increase in thrombus formation.

View full abstract

Exertional dyspnea, a major symptom of patients with chronic heart failure, mainly stems from an abnormally high ventilatory response to exercise. However, there has been considerable controversy surrounding the mechanisms of respiratory control during exercise, especially regarding the role of serum potassium. We investigated the relation between serum potassium concentration [K⁺] and ventilation (VE) during exercise before and after oral supplements of potassium chloride in cardiac patients. Thirteen patients with chronic heart disease performed a 6-min constant-work-rate exercise (65.8±11.1W) with respiratory gas measurements before initiating oral supplements of potassium chloride, 4 weeks after continued supplements, and 4 weeks after discontinuing supplements. Blood was sampled from a forearm vein at rest before exercise and at the end of exercise for measurement of [K⁺] and blood gases. The [K⁺] at rest was 3.66±0.30 mmol/L before oral supplements of potassium and significantly increased to 4.08±0.31 mmol/L (p<0.01) after supplements. In spite of the significant increases in the [K⁺], resting VE was not changed. While serum [K⁺] during exercise was significantly higher after potassium supplements than before, exercise VE was not influenced by the changes in [K⁺] throughout the study period. The findings of the present study strongly suggest that the chronic increase in the serum [K⁺] has no influence on the resting or exercise VE in patients with heart disease.

View full abstract

The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100μg) and then an ER test (40-64μg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8±0.8) was significantly lower than that of patients in group I (7.0±5.3, p<0.01) or II (3.5±2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.

View full abstract

To evaluate coronary microvascular function and its relation to the genesis of chest pain and ST-segment depression during exercise in patients with syndrome X, pacing-induced changes in transmural myocardial blood flow distribution were quantitatively assessed by 2-dimensional myocardial contrast echocardiography. Of 25 patients with a history of chest pain and normal coronary arteries with the negative ergonovine test, 11 had exercise-induced chest pain and ST-segment depression (syndrome X), and 14 did not (controls). Myocardial blood flow distribution before and after pacing stress was assessed by measuring the ratio of the endocardial to epicardial gray level (ie, endo/epi gray level ratio) in the territory of the left anterior descending coronary artery. Pacing-induced chest pain and ST-segment depression were observed in syndrome X, but not in controls. The endo/epi gray level ratio in syndrome X significantly decreased after pacing (from 0.98±0.10 to 0.76±0.17, p<0.01), but not in controls (from 0.97±0.08 to 0.99±0.08, NS). Abnormal myocardial blood flow distribution may play an important role in exercise-induced chest pain and ST-segment depression in these patients.

View full abstract

In chronic Q-wave myocardial infarction, QT dispersion is closely correlated with infarct size, but this correlation has not been evaluated for acute myocardial infarction (AMI). The effects of abnormal fatty acid metabolism on QT dispersion were examined in 123 patients with AMI who underwent resting iodine-123-15-iodophenyl 3-methyl pentadecanoic acid (BMIPP)/thallium-201(²⁰¹Tl) myocardial single photon emission computed tomography (SPECT) and electrocardiographic analysis in the subacute phase. The relationship between BMIPP and ²⁰¹Tl was defined as match when the total defect score for BMIPP was equal to or smaller than for ²⁰¹Tl, and as mismatch when the total defect score for BMIPP was larger than that for ²⁰¹Tl. Twenty-six patients (21%) demonstrated BMIPP-²⁰¹Tl match and 97 (79%) demonstrated mismatch. Infarct size was closely correlated with QT dispersion (r=0.67, p<0.001) in patients with BMIPP-²⁰¹Tl match, but weakly correlated (r=0.30, p<0.005) in patients with BMIPP-²⁰¹Tl mismatch. For small infarctions, QT dispersion was significantly larger in patients with BMIPP-²⁰¹Tl mismatch than in those with BMIPP-²⁰¹Tl match (62±24 ms vs 41±18 ms, p=0.03), but did not differ between the 2 groups for large infarctions. This study shows that QT dispersion is influenced by infarct size and by the presence of metabolically ischemic but viable myocardium in patients with AMI.

View full abstract

The efficacy of a short atrioventricular (AV) delay in patients with dilated cardiomyopathy has been reported, but there are deleterious effects of right ventricular pacing. Diastolic mitral regurgitation (MR) is observed in patients with elevated left ventricular end-diastolic pressure and can be induced by prolonging the AV delay in patients with DDD pacemakers. The critical PQ interval that induces diastolic MR may represent the upper limit of the optimal PQ interval. The efficacy of AV sequential pacing and diastolic MR were studied in 11 patients (68.3±13.7 (SD) years old) with intrinsic AV conduction and with implanted DDD pacemakers. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter and transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 ms starting from 65 ms. Pacing rate was fixed at 70-80 beats/min. In 6 of the 11 patients, diastolic MR was observed under atrial pacing and the critical PQ interval for the appearance of diastolic MR was 0.22±0.04s. CO was increased from 3.8±0.8 to 4.3±0.9 L/min (p<0.05) and PCWP was decreased from 7.5±2.8 to 5.5±1.6 mmHg (p<0.05) by shortening the AV delay till the diastolic MR disappeared. On the other hand, in 5 of the 11 patients, diastolic MR was not observed, and CO (4.2±0.5 to 4.3±0.5 L/min, ns) and PCWP (5.8±4.6 to 5.4±3.9 mmHg, ns) were not improved by AV sequential pacing. In conclusion, cardiac function may be improved by AV sequential pacing and setting the AV delay under the critical PQ interval for the appearance of diastolic MR when the diastolic MR is observed. However, AV sequential pacing may be either ineffective or even deleterious for patients in whom diastolic MR is not observed.

View full abstract

Holter monitoring is widely used for the detection of arrhythmia and ischemic episodes. Traditionally, analog amplitude-modulated Holter devices have been used for detecting arrhythmia, but they produce signal distortion due to contour effects and phase distortion caused by the tape recorders. A digital Holter device without these disadvantages has been developed and can reproduce clinically accurate electrocardiographic waveforms useful for assessment of arrhythia and ST segments. However, their reliability is questionable when detecting pacing pulses in pacemaker patients. Because electrocardiographic signals are digitized based on sampling rate, pacing pulses are occasionally missed. Therefore, the FM-300 was developed, a new device for detecting pacing pulses on digital recordings that has both digital and analog circuits in one system and indicates pacing pulse timing with arrows. This device can automatically detect and recognize pacing pulses from various artifacts and pacing modalities, making it easy to identify pacing pulses on digitally recorded electrocardiograms. The FM-300 is useful in the diagnosis and assessment of pacemaker function and has improved the reliability of pulse detection in digital Holter monitoring.

View full abstract

Some electrocardiographic variables, including the degree of maximal ST-segment depression (STD), may not necessarily indicate the severity of exercise-induced myocardial ischemia. The present study examined whether maximal STD correlates with the severity and extent of exercise-induced myocardial ischemia, as assessed by thallium-201 (²⁰¹Tl) imaging, and which parameter of exercise testing reflects scintigraphic severity and extent in 270 patients who had a 1 mm or greater horizontal or down-sloping STD on exercise ²⁰¹Tl imaging. The scintigraphic severity and extent of exercise-induced ischemia was assessed and correlated with maximal STD, number of positive leads, workload, peak heart rate, peak systolic blood pressure (SBP), rate-pressure product, chest pain and the Duke treadmill score. Most of the scintigraphic markers of the severity and extent of ischemia had significant but weak correlation with all of those parameters. Multivariate analysis demonstrated that peak SBP and the Duke treadmill score (chest pain in only simple variables model) correlated independently with scintigraphic severity and extent of ischemia. Furthermore, most of the patients with a peak SBP of 200 mmHg or more had milder and less extensive ischemia. In patients with exercise-induced STD, the scintigraphic severity and extent of ischemia may be estimated by peak SBP and the Duke treadmill score.

View full abstract

The importance of the cell cycle in proliferating cells is well known, but little is known about the role of cell cycle regulatory proteins in cardiac myocytes, which are fully differentiated cells. The present study determined, in vitro, the effect of angiotensin II (Ang II) treatment of neonatal rat cardiac myocytes on protein levels of cyclins and retinoblastoma gene product (pRb) phosphorylation. The role of G₁ cyclin/cdk in Ang II-induced cardiac myocyte hypertrophy by overexpressing cdk inhibitor p21^Cip1/Waf1 or p16^INK4a was also examined using recombinant adenoviral vectors encoding these genes. Western blot analysis revealed that Ang II stimulated cyclin D1, D2, D3 and A protein levels in cardiac myocytes. Moreover, Ang II phosphorylated pRb on serine 780, which is known to occur in mitotic cells during cell cycle progression. Cultured cardiac myocytes treated with Ang II and infected with either control or recombinant adenovirus indicated that expression of p21 and p16 inhibited Ang II-induced cardiac myocyte hypertrophy, [³H]leucine incorporation into total cellular proteins, and skeletal α-actin (SK-A) and atrial natriuretic peptide (ANP) mRNA accumulation. Control virus had no effects on these parameters. These results suggest that G₁ cyclins play an important role in cardiac myocyte hypertrophy stimulated by Ang II.

View full abstract

The 4-aminopyridine (4-AP)-sensitive transient outward current (I_to) has been reported to play an important role in the ischemia-or high [Ca²⁺]_o-induced reentrant ventricular arrhythmias. However, the role of 4-AP sensitive I_to in reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode solution (control), and treated with 0.5 μmol/L verapamil, 1 μmol/L glibenclamide, 10 μmol/L E-4031 or 2 mmol/L 4-AP. After a 10-min perfusion, hearts were subjected to 30-min global ischemia followed by 10-min reperfusion. The effects of the ion-channel blockers on the incidence of ventricular tachycardia (VT), torsades de pointes (Tdp) and ventricular fibrillation (VF) during the reperfusion period were investigated. Verapamil and 4-AP abolished VF and Tdp. The incidence of VT was also attenuated by verapamil, but not by 4-AP. Glibenclamide and E-4031 (a blocker of a rapidly activating component of delayed rectifier K⁺ current) did not affect the incidence of those tachyarrhythmias. Accordingly, (1) the underlying mechanism of VF or Tdp is different from that of VT, and (2) 4-AP sensitive I_to is required for the occurrence of reperfusion Tdp or VF in the present model.

View full abstract

The effects of chronic renal failure on cardiac performance and myocardial morphology were studied in rats: 17 with 5/6 nephrectomy (CRF rats) and 12 with sham operation (controls). Cardiac function was assessed 8 weeks postoperatively, using the Langendorff technique for an isolated working heart model. After the hemodynamic study the hearts were fixed for electron and light microscopy. In the CRF rats left ventricular systolic pressure was significantly higher at all preloads (10-20 cmH₂O) and afterloads (70-90 cmH₂O), and left ventricular stroke work was significantly increased at preload 20 cmH₂O with afterloads 70 or 90 cmH₂O. Light microscopy revealed fibronecrotic lesions consisting of fibroblastic proliferation with newly formed collagen interposed between or entrapping degenerative myocytes. The changes were focally distributed, with perivascular accentuation and were most frequent in the basal half of the ventricular wall. Electron microscopy of non-necrotic myocytes showed intact myocytes, with mitochondria morphometrically similar in the 2 groups, but a significantly lower incidence of mitochondrial granules in the CRF rats. Thus 8 weeks of CRF showed no cardiac dysfunction associated with the focally distributed fibronecrotic myocardial lesions and decrease in mitochondrial granules. The precise mechanism of the discrepancy between the morphological change and the cardiac function is unclear. One possible explanation may be that because the pathological changes in the myocardium were focal or mild to moderate, some compensation mechanism may be involved or it may be the turning point of functional change from acute renal failure to the chronic state.

View full abstract

Heart transplantation is increasingly becoming accepted worldwide as therapy for end-stage heart failure not only in adult patients but also in pediatric practice. The new law in Japan for organ transplantation from brain-dead patients was established on 16 October 1998, but there is no definite law or protocol for brain death in children under the age of 6 years and children less than 15 years of age cannot become donors. These facts make organ transplantation from the cadavers of neonates, infants and young children almost impossible in Japan, even though there are children who need heart or heart-lung transplantation. The present authors have to date transferred 8 patients to the USA or Germany for heart transplantation: 4 successfully underwent heart transplantation, but 4 died during the waiting period overseas. There are many things to consider; not only the medical problems involved in transportation, but also the financial issues when transferring patients to other countries. This report details the experience with the 8 cases that were transferred overseas for heart transplantation, and highlights the problems that need to be considered.

View full abstract

Hepatitis C virus (HCV) infection is frequently associated with autoimmune disease. We present here a case of dermatomyositis manifested as heart failure in which HCV was detected from an endomyocardial biopsy sample. HCV infection may have contributed to the left ventricular dysfunction in this patient with dermatomyositis.

View full abstract

This report describes a case of cardiac tamponade as the initial manifestation of unclassified connective tissue disease (UCTD). A 68-year-old Japanese woman was admitted to hospital because of dyspnea and edema. She had undergone a radical left mastectomy for the treatment of breast cancer 18 years before. On admission, bilateral leg edema, hepatomegaly, and a paradoxical pulse were noted on physical examination. The erythrocyte sedimentation rate was elevated and the C-reactive protein was 2.8mg/dl. Antinuclear antibodies and anti-SS-A/Ro antibodies were present. The scl-70 and anticentromere antibodies were elevated. Chest radiography showed cardiomegaly. Echocardiography revealed a large pericardial effusion, but the pericardial fluid did not contain malignant cells or bacteria. She did not meet the diagnostic criteria for any known connective tissue diseases, so was diagnosed with cardiac tamponade due to UCTD. Prednisolone (30mg/day) was administered, which resulted in a gradual resolution of the pericardial effusion. Although connective tissue diseases are known to cause pericardial effusion, cardiac tamponade as the initial manifestation of the disease in the absence of other symptoms is quite rare.

View full abstract

This paper reports a case of dilated phase in hypertrophic cadiomyopathy with mid-ventricular obstruction. Following the first cardiac catheterization and endomyocardial biopsy, the patient was diagnosed as having hypertrophic cardiomyopathy (HCM) with mid-ventricular obstruction. He had been first diagnosed at the age of 38 years and was subsequently followed for 20 years. Echocardiogram revealed gradually progressive dilatation of the left ventricle, associated with disappearance of the mid-ventricular obstruction. The second cardiac catheterization and endomyocardial biopsy performed at the age of 58 disclosed that the patient was in the dilated phase of HCM with a dip-and-plateau pattern diastolic pressure trace.

View full abstract

A 64-year-old woman presented with right heart failure caused by a cardiac tumor centered in the free wall of the right ventricle, accompanied by pericardial effusion. A match between the biopsy specimen and tissue removed 4 years earlier resulted in the diagnosis of a cardiac metastasis from a chordoma. Immunohistochemical staining was also useful in establishing the diagnosis. To alleviate the right ventricular outflow obstruction, a palliative operation was planned, resecting the tumor and performing a right ventriculoplasty, which was cancelled due to the extent of infiltration of the tumor, and instead a right atrium to pulmonary artery shunt was attempted using a vascular prosthesis, only to fail due to an inability to maintain blood flow through the prosthesis. Presently there are no definitive treatment options available, and some palliative chemotherapy is being performed. Single cardiac metastases from a chordoma are extremely rare.

View full abstract

A 65-year-old woman was admitted to hospital because of orthopnea. She had been followed-up for chronic pericardial effusion detected by echocardiography 10 years previously. Initial echocardiography showed that the left ventricular diastolic diameter (LVDd) was 39 mm and percent fractional shortening (%FS) was 33.3%. Neither fluid samples nor a pericardial biopsy specimen identified the etiology. Cardiac tamponade was not evident, and C-reactive protein and creatine-kinase values were within normal limits. During follow-up, the %FS decreased gradually, but the LVDd remained unchanged. On admission, echocardiography showed that the %FS was 12.5% and LVDd was 40mm. She developed intractable hyponatremic heart failure with bilateral pleural effusion. Autopsy findings revealed that infiltration of small lymphocytes in the epicardium had penetrated into the subepicardial myocardium. The subepicardial myocardium and the interventricular septal myocardium were diffusely replaced by fibrosis, which could have induced restrictive diastolic heart failure and reduced left ventricular contractility. The fibrosis was not detected in the epicardium itself nor the subendocardial myocardium. This is the first report describing diffuse subepicardial myocardial fibrosis in a patient with chronic pericardial effusion and progressive heart failure.

View full abstract

A 49-year-old man was referred for further treatment of sustained monomorphic ventricular tachycardia (VT) associated with cardiac sarcoidosis. During an electrophysiologic study (EP), dl-sotalol suppressed the spontaneous VT and prevented induction of VT. However, when predonisolone treatment was started, monomorphic VT recurred frequently. To terminate the VT, a temporal pacing lead was placed at the apex of the right ventricle, and programmed electrical stimulation was attempted from the lead. During the EP study, 2 different monomorphic VTs were repetitively induced and both types were able to be terminated by rapid ventricular pacing; in one of the VT morphologies, constant and progressive fusion was obvious during the ventricular pacing. Some monomorphic VTs associated with cardiac sarcoidosis are due to reentry with an excitable gap, but the clinical efficacy of EP-guided antiarrhythmic drug treatment seems to be less certain during steroid therapy. In the present case, a defibrillator device was implanted to prevent a possible arrhythmic event.

View full abstract

Transthoracic echocardiography or transesophageal echocardiography is sometimes useful in intracardiac tumor biopsy. Intracardiac echocardiography was used as an alternative to either of these for performing a biopsy of a right cardiac tumor in a 79-year-old woman. The procedure was well tolerated and no complications occurred. Histopathological findings and immunohistological staining were compatible with the diagnosis of neurogenic sarcoma.

View full abstract

A 56-year-old Japanese woman with an acute inferior myocardial infarction was admitted to hospital. Emergency coronary angiography revealed an anomalous origin of the right coronary artery from the left sinus of Valsalva, but there was no stenosis or thrombus in either the right or left coronary artery. Coronary spasm was provoked at the site of the proximal portion of the anomalous coronary artery, which was located between the aorta and pulmonary trunk. This was thought to be the cause of the myocardial infarction.

View full abstract

Three-dimensional images of the coronary arteries using electron-beam computed tomography (EBCT) data with shaded surface rendering makes it possible to achieve images easily with a short reconstruction time. However, a lower threshold is required to estimate vessel diameters and there is a quantitative problem compared with conventional coronary arteriography. In combination with volume rendering, EBCT may be useful to detect the normal coronary artery wall, the major components of the atherosclerotic plaque (lipid, fibrous connective tissue and calcium). EBCT scans offer a new, non-invasive alternative to conventional coronary arteriography for diagnosis of coronary artery disease.

View full abstract