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EAT/mcl-1 (EAT), a bcl-2-related immediate early gene, is up-regulated at an early stage of differentiation of human embryonal carcinoma cells. Recent studies have revealed that EAT inhibits apoptosis both in vitro and in vivo. In the present study, we demonstrated that the EAT gene was up-regulated in the early stage of rat myocardial infarction. This pattern of up-regulation was apparently different from that of another immediate early gene, c-fos. EAT, an anti-apoptotic molecule, was strongly up-regulated in the non-ischemic region. In contrast, the expression of c-fos was induced in both ischemic and non-ischemic regions, and was higher in the ischemic region. Apoptosis of cardiomyocytes is currently thought to significantly contribute to acute myocardial infarction. We detected cardiomyocyte apoptosis by gel electrophoresis of genomic DNA and in situ nick end labeling in the ischemic region, but not in the non-ischemic region. As an inhibitor of apoptosis, EAT may play a role in the protection of cardiomyocytes in the early stage of acute myocardial infarction.

The present study investigated whether regional ventricular dyskinesia (ie, systolic bulging) is a direct cause of ST-segment elevation in canine hearts in vivo. Regional ventricular dyskinesia was induced in 33 anesthetized open-chest dogs by injection of negative inotropic agents into the left anterior descending coronary artery (LAD) without disruption of coronary blood flow. Regional myocardial contraction was assessed in terms of the percent systolic shortening (%SS) and percent systolic bulging (%bulging), which were measured using ultrasonic crystals. The ST-segment elevation of the LAD-perfused area was measured with a unipolar electrode. Lidocaine, a sodium channel blocker, nicorandil, a potassium channel opener, propranolol, a beta-adrenergic blocker, or verapamil, a calcium channel blocker, was administered by intracoronary injection during maximal vasodilation induced by adenosine. All drugs induced dose-dependent ST-segment elevation in association with a parallel reduction in %SS and a parallel increase in %bulging. The absence of myocardial ischemia was confirmed by the absence of NADH fluorescence. It was concluded that regional ventricular dyskinesia had an important role in ST-segment elevation not associated with myocardial ischemia.

We examined the effectiveness of Palmaz-Schatz (P-S) stent and directional coronary atherectomy (DCA) in ostial lesions of left anterior descending arteries (LAD). The P-S stent was implanted in 11 cases at LAD ostial lesions, and DCA was performed in 13 cases. Percent stenosis and vessel diameter at the target site and the ostium of the circumflex coronary artery (LCX) were measured before and after the procedure. The initial success rate was 100% in both groups. No major complication occurred. LAD ostial lesions were improved from 81.3+/-3.4% to -8.1+/-5.7% by P-S stent and from 82.8+/-2.6% to -2.7+/-3.9% by DCA. LCX ostial vessel diameter was not changed by DCA (from 3.0+/-0.2 mm to 3.1+/-0.3 mm); however, it was significantly decreased by P-S stent (from 2.9+/-0.2 mm to 2.6+/-0.2 mm, P0.01). When the angle of LAD and LCX wasor = 80 degrees from the view of RAO 30 degrees and Caudal 30 degrees, the LCX ostium was significantly narrowed by stenting at LAD ostium (P0.01). These findings indicate that both the P-S stent and DCA are effective and safe therapies for LAD ostial lesions in cases with LAD-LCX angle80 degrees. In cases with LAD-LCX angleor = 80 degrees, however, DCA is a favored therapy rather than P-S stenting to avoid narrowing of the LCX ostium.

The purpose of this study was to evaluate ST-segment elevation induced by regional myocardial stretch without myocardial ischemia in canine hearts. A strain gauge arch (TH-601T) was sutured to the left ventricular epicardium, parallel to the short axis, to shorten the end-diastolic length of the myocardium beneath the arch (stretch zone; SZ) and to produce regional myocardial stretch in each of 6 dogs. An increase in preload caused by altering the height of a saline-filled reservoir affected prolongation or shortening of the myocardium both in the SZ and outside the arch (normal zone; NZ) to increase myocardial stretch. An epicardial electrocardiogam was recorded in both the SZ and the NZ. After suture of the strain gauge arch, the ST segment was elevated in the SZ. An increase in preload augmented stretch during systole in the SZ, resulting in additional ST-segment elevation. These results suggest that regional myocardial stretch itself plays an important role in ST-segment elevation. (Jpn Circ J 1997; 61: 921 - 926)

complaining of palpitation Yoshiyasu Aizawa ⁎, Seiji Takatsuki , Yuko Suenaga , Takehiro Kimura , Nobuhiro Nishiyama , Kotaro Fukumoto , Yoko Tanimoto , Kojiro Tanimoto , Shun Kohsaka , Yukiko Fukuda , Mitsushige Murata , Shunichiro Miyoshi , Toshiaki Sato , Shiro Iwanaga , Satoshi Ogawa , Keiichi Fukuda a a Keio University School of Medicine, Tokyo, Japan b Kyorin University, Tokyo, Japan c Tokyo Medical University, Tokyo, Japan d International University of Health and Welfare, Mita Hospital, Tokyo, Japan

The elevation of aortic pressure increases myocardial oxygen consumption and increases the blood supply to the myocardium. It is not obvious whether elevated systemic arterial pressure would enhance or diminish myocardial protection during acute myocardial ischemia. This report reviews previously published data on the effects of aortic pressure elevation on the coronary pressure-flow relationship, and on the ischemic myocardium in the dog. The shift of the maximally-dilated coronary pressure-flow line to the right on the pressure-flow diagram is an indication of the deterioration of the oxygen supply/demand ratio caused by aortic pressure elevation. The only maneuver recognized for protecting the ischemic myocardium is early reperfusion. In patients with de novo acute myocardial ischemia, we propose that myocardial protection can be enhanced by reduction of systemic blood pressure until coronary reperfusion therapy is initiated.

Accessory mitral valve tissue is a membranous or tumor-like structure observed in the left ventricular outflow tract. This congenital anomaly has been reported in more than 100 cases since 1842; however, most of them were found in patients with complex cardiac malformations. We report a 72-year-old Asian woman with isolated accessory mitral valve tissue incidentally found during the evaluation of hypertension and arrhythmia. Her left ventricular outflow tract obstruction was mild. Because worsening of the left ventricular outflow tract obstruction was reported in patients without significant obstruction at the time of diagnosis, periodical echocardiographic follow-up is necessary.

Mitral valve prolapse (MVP) is usually benign, although serious complications may occur. It remains unclear whether the region of prolapsed mitral leaflets might affect prognosis. The aim of this study was to investigate lesional differences of clinical courses of MVP.We retrospectively investigated 128 MVP patients who had been followed up for for a mean of 56.4 months. They were classified into prolapse of the anterior mitral leaflet (AML, n = 59), posterior mitral leaflet (PML, n = 47), or both leaflets (AMLPML, n = 22). Echocardiographic and clinical data were examined from medical records. Average time to clinical events; MV surgery, new onset of atrial fibrillation (AF), echocardiographic evidence of new chordal rupture, and worsening of mitral regurgitation severity were all significantly shorter in PML prolapse than in those with AML or AMLPML prolapses. Increases in the left ventricular dimensions and estimated pulmonary arterial systolic pressures were significantly larger in PML prolapse, compared with AML or AMLPML prolapses. A subanalysis of PML prolapse revealed that new chordal rupture tended to be more frequent in middle scallop prolapse (48%) compared with lateral and medial scallops (18%). In contrast, new onset of AF tended to occur in lateral and medial scallop prolapses (44%) compared with middle scallop prolapse (20%).PML prolapse patients had a poor outcome, compared with AML or AMLPML prolapse patients. Precise regional evaluation of the prolapsed leaflets may predict cardiac complications in MVP.

We measured the QRS duration during a treadmill exercise test and the QT interval using a 24-hour Holter electrocardiogram at various heart rates to identify use-dependent QRS prolongation and reverse use-dependent QT prolongation of class I and III antiarrhythmic drugs. Use-dependent QRS prolongation was detected in 61%, 53%, and 64% of patients receiving disopyramide, mexiletine, and pilsicainide, respectively. Reverse use-dependent QT prolongation was found in 40% and 70% of patients receiving disopyramide and E4031. Drugs suppressedor = 75% of the total premature ventricular contractions in all patients who had both use-dependent QRS prolongation and reverse use-dependent QT prolongation, in 79% of patients with use-dependent QRS prolongation alone, in 70% with reverse use-dependent QT prolongation alone, and in 11% with neither use-dependent QRS prolongation nor reverse use-dependent QT prolongation. Use-dependent QRS prolongation and reverse use-dependent QT prolongation were identified noninvasively and were useful in evaluating antiarrhythmic efficacy.

Magnetic resonance imaging (MRI) is considered the clinical reference standard for measuring the right ventricular (RV) volume and ejection fraction, although real-time 3-dimensional echocardiography (RT3DE) would be a preferred method owing to its convenience and availability for repetitive examinations. However, the feasibility, accuracy, and reproducibility of RT3DE have not been fully examined. The present study sought to validate the correlation of RT3DE with a 2-dimensional summation method compared to MRI for assessing the function of the right ventricle and to evaluate the RV function in patients with pulmonary hypertension (PH). Thirty patients with PH underwent both RT3DE and MRI. The right ventricle was reconstructed with RT3DE using a 2-dimensional summation method to analyze the MRI measurements. The RV end-diastolic volume, RV end-systolic volume, and RV ejection fraction were measured. Fifteen normal subjects underwent the same echocardiographic protocol for comparison. The RV end-diastolic volume index, RV end-systolic volume index, and RV ejection fraction measured using RT3DE correlated well with those measured using MRI (R = 0.96, p0.001; R = 0.96, p0.001; p = 0.93, and p0.001, respectively). All inter- and intraobserver variability values for the RV end-diastolic volume, RV end-systolic volume, and RV ejection fraction were17%. Both the RV end-diastolic volume index and the RV end-systolic volume index were significantly enlarged in those with PH compared to those in the normal subjects (RVEDVI 123 ± 42 ml/m² vs 74 ± 12 ml/m²; RVESVI 86 ± 33 ml/m² vs 26 ± 5 ml/m² in those with PH and the normal subjects, respectively, p0.0001). In contrast, the RV ejection fraction was significantly reduced in the patients with PH compared to that in the normal subjects (30 ± 12% vs 65 ± 6%, respectively, p0.01). Thus, RT3DE with a 2-dimensional summation method might provide comparable and feasible measurements of the RV volume in patients with PH compared to MRI.

In patients with active infective endocarditis mitral valve repair is better than mitral valve replacement, but it remains a challenge when there has been massive destruction of the rough zone of the anterior leaflet. We report a technical modification of mitral valve repair for advanced active infective endocarditis in which a widely infected rough zone and the chordae were successfully replaced with autologous pericardium and multiple artificial chordae. The procedure described here is capable of improving the prospects of mitral valve repair in advanced infective endocarditis.

Loeffler endocarditis is a serious complication of idiopathic hypereosinophilic syndrome (HES) characterized by a peculiar type of fibrosing endomyocarditis [1]. It results in various cardiac disorders and systemic embolism due to intracardiac thrombus, and these manifestations are the major causes of morbidity and mortality. Although there is still no definite therapy for Loeffler endocarditis and the prognosis is poor with high mortality rates, steroid therapy may be effective if treated at the appropriate period. Echocardiography is a mandatory evaluation in HES patients and useful to detect cardiac manifestations. A 33-year-old man with medical history of pulmonary embolism and hepatitis B was admitted to our institution with activity-induced dyspnea and systemic edema. An abnormal blood eosinophil count (1820 per lL) was also reported. Bone marrow was normocellular on examination. Echocardiography demonstrated the presence of pronounced biventricular apical thrombi, and enlarged atriums with normal LV dimension and ejection fraction (Fig. 1). Transmitral flow pattern was restrictive with increased E/A ratio (4.3) and shortened deceleration time (85 ms). Cardiac catheterization demonstrated markedly elevated biventricular end-diastolic pressure, which differed by 11 mmHg, as well as pulmonary artery pressure of 55 mmHg with a normal LV ejection fraction of 63 % (Fig. 2). These hemodynamics were consistent with restrictive cardiomyopathy. Endomyocardial biopsy remains the diagnostic gold standard, because only biopsy can detect endocardial infiltration. Thus, despite the iatrogenic complications such as embolism, endomyocardial biopsy was performed, revealing infiltration of eosinophils into the myocardium. Together, these findings confirmed a diagnosis of Loeffler endocarditis. Oral anticoagulation with Coumadin and high-dose steroid therapy was promptly initiated, resulting in improvement of clinical symptoms and reduction of E/A ratio (4.3 to 3.0).

[Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4] A 29-year-old asymptomatic man was referred to our hospital for treatment of Crohn's disease. Before commencing treatment, the patient underwent a cardiac assessment. An echocardiogram showed a localized low-echoic cavity with a

Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed. There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE). In the NVE group there were 175 clinically active patients and 10 non-active patients. The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively. Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage. Patients with embolism showed significantly higher mortality. Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis. In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died. Indications for operation were intractable cardiac failure, uncontrollable infection and angina. In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively. The only survivor was a patient operated early under stable hemodynamics. These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection.

On rare occasions, extrinsic compression of the coronary artery can cause significant stenosis. We report a 42-year-old woman who was referred to our hospital for surgical repair of atrial septal defect. Cardiac 64-slice multi-detector computed tomography before the operation revealed the extrinsic compression of the proximal left main coronary artery by the marked dilatation of pulmonary trunk. The patient eventually underwent atrial septal defect closure and coronary artery bypass simultaneously. Four months after the operation, multi-detector computed tomographic scan revealed reduction of pulmonary trunk diameter and resolution of left main coronary artery narrowing.

The venous blood flow in the great cardiac vein (GCV) was meas-ured with an ultrasonic transit-time flowmeter during brief occlusion of major branches of the coronary arteries in open-chest dogs. Occlusion of the right coronary artery did not affect GCV outflow. GCV outflow vanished when the left anterior descending artery (LAD) was occluded proximal to the bifurcation of the septal artery. When the LAD was occluded distal to the septal artery, the GCV flow reduction averaged 70%. Occlusion of the left circumflex artery resulted in a slight but significant decrease, followed by an increase in GCV outflow. Partial occlusion of the coronary sinus or GCV by a catheter resulted in a decrease in outflow. This suggests that the absolute value of coronary venous flow obtained by the thermodilution technique should be evaluated carefully.

Genetic variation, a −1327T/C polymorphism, of human telomerase reverse transcriptase (hTERT) is associated with leukocyte telomere length in healthy subjects, but clinical significances of this functional polymorphism are not clear. Recently, the relationship between the telomere system and coronary artery disease (CAD) was reported. We investigated the association between the −1327T/C polymorphism and (a) susceptibility to CAD and (b) telomere length in CAD patients. In a case-control study, 104 patients confirmed by coronary angiography and 115 age- and sex-matched controls were enrolled. There was a higher frequency of the −1327C/C genotype in CAD patients (51.9%) compared with controls (36.5%, p = 0.0218). Among the 104 CAD patients, leukocyte telomere length in the −1327C/C genotype (7.62 ± 2.19 kb, mean ± SD) was shorter than that in the −1327T/C and −1327T/T genotypes (8.74 ± 2.92, p = 0.0287). These findings suggest that the −1327C/C genotype is a genetic risk factor for CAD and relates to shorter telomere length among CAD patients.

Apoptosis of cardiomyocytes plays an important role in reperfusion injury following myocardial infarction. Conversely, interleukin-6 (IL-6)--a potent cytokine--inhibits myeloma cell apoptosis by activating GP130 through the IL-6 receptor (IL-6R). We hypothesized that the IL-6/soluble IL-6R complex can inhibit myocardial apoptosis, and limit infarct size in reperfused acute myocardial infarction. Anesthetized rats were randomly divided into five groups: sham, coronary occlusion and reperfusion rats administered IL-6/soluble IL-6R complex, IL-6 alone, soluble IL-6R (sIL-6R) alone, or a control vehicle. Rats were subjected to 30 min occlusion of the left coronary artery followed by 3 h reperfusion. After reperfusion, the hearts were excised. For detection and quantification of apoptosis, gel electrophoresis of extracted genomic DNA and TUNEL method of paraffin sections were performed. The percentage of the infarct area was measured using tetrazolium chloride staining. The cardiomyocyte apoptosis analysis revealed that apoptosis in the reperfused myocardium was inhibited only in the complex group. Furthermore, the percentage of the infarct area out of the area at risk was remarkably reduced in the complex group (23.8+/-1.8%), compared with that in the vehicle (37.9+/-3.7%), the IL-6 (40.7+/-1.0%), or the sIL-6R (37.5+/-2.4%) groups (P=0.0002). No significant differences were observed among the vehicle, IL-6, and sIL-6R groups. The IL-6/soluble IL-6 receptor complex inhibits cardiomyocyte apoptosis in reperfused acute myocardial infarction. It possibly reduces irreversible reperfusion injury.

Study objectives Most left ventricular (LV) thrombi that occur after acute myocardial infarction (AMI) are formed within 2 weeks, when inflammatory cells have infiltrated into the necrotic myocardium. Inflammatory changes on the endocardial surface may induce platelet deposition and fibrin net formation through interaction with proinflammatory cytokines. We sought to determine the significance of the inflammatory response reflected by serum C-reactive protein (CRP) elevation in LV thrombus formation after AMI. Design We examined 160 patients with first anterior AMI. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. Echocardiography was performed 10 to 14 days after the onset. We assessed the association between the elevation of serum CRP levels and LV thrombus formation after AMI. Results LV thrombus was observed in 13 patients (8%). There was no difference in age, sex, coronary risk factors, preinfarction angina, use of revascularization therapy and anticoagulant therapy, platelet count, and fibrinogen level on hospital admission between the two groups. The mean (± SD) peak serum CRP level was markedly increased in patients with LV thrombus compared to those without (18.0 ± 12.6 vs 9.4 ± 8.1 mg/dL; p=0.001), despite their having similar peak CK levels. Multivariate analysis showed that a peak CRP level of ≥ 20 mg/dL was an independent predictor of thrombus formation (relative risk, 4.82; p=0.037) among variables including older age (≥ 60 years old), peak CK level (≥ 3,000 IU/L), and peak WBC count (≥ 12,000 cells/μL). Conclusion A greater elevation of serum CRP level was associated with a higher incidence of LV thrombus after AMI, suggesting an important role of the inflammatory response in mural thrombus formation.

EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1 alpha promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 -- possible heterodimeric partners for EAT in the anti-apoptotic process -- were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.

A 55-year-old Asian man first visited to our hospital with complaining of exertional dyspnea eight years ago, and was diagnosed as having idiopathic dilated cardiomyopathy. One of his siblings also suffered from idiopathic dilated cardiomyopathy. His symptoms became worse gradually, and he was hospitalized again because of disturbance of consciousness on February 21, 2001. Hemodynamic monitoring with a Swan-Ganz catheter was started, which revealed that the cardiac index was 1.1 L/ min/BSA, cardiac output 1.8 L/min, and pulmonary artery pressure 43/33 mmHg. The echocardiographic observation showed that the left ventricular ejection fraction was 32%, and serum BNP was elevated to 5,411 pg/mL. Multi-organ failure including renal and hepatic dysfunction developed because of the low cardiac output status. Continuous hemodiafiltration (CHDF) was introduced to reduce the volume overload, improve renal failure, and eliminate adverse cytokines. Although his hemodynamic status was temporarily improved after starting CHDF, weaning from CHDF was difficult and he finally died from cardiogenic shock after two month of intensive therapy. The autopsy showed thinning of the left ventricular wall, and histological examination revealed diffuse fibrous hyperplasia and myocardial fiber deficit in the ventricular myocardium. CHDF was effective in reducing the volume overload and improving renal function; however, heart transplantation is inevitable for the patients with severe heart failure due to dilated cardiomyopathy.

Few previous reports have comprehensively screened all the anti-myocardial autoantibodies (AMCA) in relation to other clinical profiles in patients with idiopathic dilated cardiomyopathy (IDC), so the present study used both immunohistochemistry (FITC) and immunoblotting (IB) for screening patients with IDC in order to characterize the clinical significance of AMCA. Sera were collected from 100 patients with IDC and age-matched 100 healthy control subjects (CTL). For FITC, an unfixed frozen section of human myocardium was used for the standard indirect immunofluorescence; for IB, total cardiac homogenates of the same myocardium were blotted to serum at 2 sets of dilution (1:200 and 1:10,000). The positive rates of AMCA detection for each method were as follows (IDC vs CTL); 39% vs 6% for FITC, 38% vs 4% for IB (1:200), and 10% vs 0% for IB (1:10,000). Fifty-nine patients with IDC and 8 CTL were positive for AMCA by either method, and 18 patients with IDC and 2 CTL were positive for AMCA by both methods. IB-positivity at 1:200 was an independent predictor by multiple logistic regression analysis of non-sustained ventricular tachycardias as well as left ventricular end-diastolic diameter and plasma norepinephrine concentration.

We describe a 52-year-old woman incidentally diagnosed as having parachute mitral valve (PMV). Echocardiography displayed a parachute-like deformity of the mitral valve characterized by a unifocal attachment of mitral valve chordae. PMV is a congenital cardiac malformation that causes stenosis of the mitral valve and is often found in combination with left-heart obstruction in the pediatric population. The incidence of PMV in adults is extremely low. This patient had no related cardiac complications, which accounts for the long asymptomatic period. Thus, rare forms of congenital heart disease in late adulthood need attention in echocardiographic study.

Regional transmural ischemia causes both ST-segment elevation and systolic elongation (bulging) of the myocardium. Mechanical stretch might alter the transmembrane potentioal via stretch-activated ion channels (SAC); however, the role of SAC on ischemic ST-segment elevation has not yet fully studied. The present study investigated the role of SAC in the genesis of ischemic ST-segment elevation in the in-vivo canine heart. In 6 anesthetized dogs, an extracorporeal conduit connected to the left anterior descending coronary artery was occluded for 5 min before and after the intracoronary infusion of gadolinium (Gd, 500 μmol/min). To eliminate the effect of ischemic preconditioning, the bypass was occluded for 5 min before the experiment. Percent systolic shortening (%SS) and percent systolic elongation (%bulging) were measured using a pair of ultrasonic dimension crystals. A unipolar epicardial ECG was monitored at the center of the ischemic area for the measurement of the ST-segment level. At the end of coronary occlusion, there was no difference in the reduction of %SS or the increase of %bulging between before and after infusion of Gd. ST-segment elevation, however, was significantly attenuated by the infusion of Gd. These data demonstrated that the activation of SAC is one cause of ischemic ST-segment elevation. (Jpn Circ J 1999; 63: 624 - 628)

Iodine-123-labelled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) is a branched fatty acid analogue for myocardial imaging, which has been recently designed for medium washout rates from the myocardium. The purpose of this study was to assess the clinical feasibility of use of 9MPA for the evaluation of myocardial ischaemia. Twenty-one patients were injected with 9MPA at rest, and sequential single-photon emission tomography (SPET) acquisitions were performed 5, 45 and 240 min after administration to calculate washout rates from the myocardium. The findings of 9MPA images were analysed in comparison with those of perfusion images with thallium-201 or sestamibi, coronary angiography and left venticulography. In general, reduction of 9MPA uptake was more remarkable than that of perfusion tracers. The findings of 9MPA early images correlated better with those of exercise perfusion images than with the rest images. Measured washout rates of 9MPA from ischaemic myocardium were significantly slower than those from normal myocardium. The majority of areas with abnormal 9MPA distribution manifested wall motion abnormality, while all areas with normal tracer distribution presented normal wall motion. The detectability of myocardial ischaemia was improved by adding mid and delayed images in six cases. However, both washout and fill-in patterns were encountered in ischaemic lesions, rendering the interpretation of images difficult. In conclusion, the results of this study indicated that 9MPA has acceptable myocardial uptake, that its use is feasible for the detection of ischaemia and that the abnormal distribution of the tracer correlates well with wall motion abnormality reflecting metabolic disorders.

This article presents two cases with preserved myocardial201Tl uptake and absent uptake of two kinds of radioiodinated fatty acids: iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methyl-pentadecanoic acid (BMIPP) and iodine-123-labeled 15-(p-iodophenyl)-9-(R,S)-methyl-pentadecanoic acid (9MPA). Although coronary angiography showed no stenotic lesion and left ventriculography revealed no wall motion abnormality, no myocardial uptake of BMIPP and 9MPA was observed in the first case. In the second case, no myocardial accumulation was recognized even in the initial phase of dynamic SPECT acquired soon after the injection of 9MPA. The results suggest that the non-visualized myocardium was not specific for BMIPP imaging and that rather than the early back diffusion of the tracers from the myocardium, abnormality of the myocardial cell membrane was a possible mechanism accounting for the phenomenon.

A practical method for scatter and attenuation compensation was employed in thallium-201 myocardial single-photon emission tomography (SPET or ECT) with the triple-energy-window (TEW) technique and an iterative attenuation correction method by using a measured attenuation map. The map was reconstructed from technetium-99m transmission CT (TCT) data. A dual-headed SPET gamma camera system equipped with parallel-hole collimators was used for ECT/TCT data acquisition and a new type of external source named ”sheet line source” was designed for TCT data acquisition. This sheet line source was composed of a narrow long fluoroplastic tube embedded in a rectangular acrylic board. After injection of 99mTc solution into the tube by an automatic injector, the board was attached in front of the collimator surface of one of the two detectors. After acquiring emission and transmission data separately or simultaneously, we eliminated scattered photons in the transmission and emission data with the TEW method, and reconstructed both images. Then, the effect of attenuation in the scatter-corrected ECT images was compensated with Chang’s iterative method by using measured attenuation maps. Our method was validated by several phantom studies and clinical cardiac studies. The method offered improved homogeneity in distribution of myocardial activity and accurate measurements of myocardial tracer uptake. We conclude that the above correction method is feasible because a new type of 99mTc external source may not produce truncation in TCT images and is cost-effective and easy to prepare in clinical situations.

Matching the supply of blood and oxygen to the myocardial demand for oxygen is an essential function of the coronary regulatory system. The heart cannot tolerate a deficit of oxygen for more than a few seconds without harmful consequences, so that the regulatory system must respond rapidly to changes in oxygen demand or perfusion pressure. The matching of oxygen supply to myocardial oxygen demand can be examined in three main ways. One of them is to test autoregulation which may be defined as the response to a change in perfusion pressure when myocardial oxygen demand remains unchanged. To do this in the heart, the coronary artery must be cannulated so that changes in perfusion pressure have no or relatively little effect on myocardial oxygen demand. The second method is to examine the response during constant perfusion pressure to changed myocardial oxygen demand which may either be increased by pacing, increases in cardiac pressure or volume work, or infusion of metabolic stimulators like calcium or catecholamines, or may be decreased by decreasing cardiac pressure or volume work or by decreasing contractility. A subset of these experiments is to examine maximal flows induced by severe exercise or very rapid pacing. The third method is to examine the reactive hyperemic response; coronary flow is stopped for several seconds, and the hyperemic response after flow is restored is examined. It is possible that all these three methods are examining the same regulatory systems, except that reactive hyperemia only examines decreases in oxygen supply and definitely produces transient ischemia.

We examined the accuracy and feasibility of using simultaneous intracoronary Doppler and two-dimensional (2D) ultrasound imaging in the measurement of volumetric coronary blood flow (CBF). A femoral artery-to-circumflex coronary artery shunt was created in four dogs with tubing that incorporated an in-line transit-time ultrasound (TTU) flow probe. A 2D ultrasound catheter was introduced over a 0.014-inch Doppler guide wire into the circumflex artery with the guide wire tip positioned 2 cm beyond the imaging catheter tip. Cross-sectional area (CSA) and average peak velocity (APV) were recorded. CBF was determined from the previously validated relation CBF = CSA x 0.5 APV and the adjusted measurement formula CBF = CSA x 0.47 APV. Within the 119 measurements made, TTU CBF varied from 31 to 385 ml/min. An excellent correlation was found between 2D/Doppler-derived and TTU CBF with both constants; measurement agreement was improved and bias minimal with the 0.47 constant (slope = 0.9997; r = 0.99; p0.0001; SEE = -6.7 +/- 8.6). We conclude that simultaneous 2D and Doppler ultrasound yields accurate estimates of volumetric CBF.

The effects of elevated aortic pressure on the pressure-flow (P/F) relationship below the pressure range of autoregulation were investigated. The effects of myocardial contraction dysfunction on coronary blood flow were also studied. In eight dogs, the left anterior descending coronary artery (LAD) was perfused by a bypass circuit from the subclavian artery. Coronary perfusion pressure (CPP) was reduced by mechanical stenosis of the bypass tube. Aortic pressure (AoP) was elevated by aortic banding. The heart rate was kept constant by SA block and pacing. Bypass flow (CoF), myocardial shortening (%SS) of the LAD region, and instantaneous diastolic P/F relation were obtained at each CPP and AoP level. When the stenosis was mild (CPP > 60 mmHg), CoF was increased by 1.2 ml/min by 10 mmHg elevation of AoP, but when the stenosis was severe (CPP < 50mmHg), CoF was reduced by 2.0ml/min by AoP elevation. The slope of P/F relation was reduced by the elevation of AoP in mild stenosis. In severe stenosis, AoP elevation increased the zero flow pressure (Pzf) and did not change the slope of the P/F relation. The %SS was significantly reduced with a rise of AoP only in severe stenosis. In five other dogs, phasic LAD flow was measured, using an ultrasonic transit time flowmeter just below the first diagonal branch. The branch was cannulated proximally to infuse adenosine (500μg/min) into the LAD to obtain maximal vasodilation. Lidocaine (0.5–4 mg) was injected into the LAD to alter the regional myocardial contraction.

Although there are some reports that have evaluated the correlation between mitochondrial tRNA(Leu) (UUR) mutation at position 3243 and cardiomyopathy, the degree of cardiac involvement in mitochondrial diabetes is still largely unknown. Here we report the case of a patient with mitochondrial diabetes who developed cardiac dysfunction, evaluated by echocardiography, along with worsening of glycemic control over a relatively short period, within a year. In April 1997, a 22-year-old Japanese man presented to a medical practice because of thirst, polyuria, and body weight loss of ∼8 kg over a few months. Because blood testing revealed a high plasma glucose level (23.6 mmol/l), and because urine was positive for ketone bodies, he was immediately admitted to the hospital. After initial therapy with insulin for 5 months, he was mainly treated with oral hypoglycemic agents. In July 1998, his glycemic control worsened and he presented to our hospital; insulin therapy was restarted. Because his maternal grandmother and paternal uncle had diabetes and he complained of hearing impairment, he was thought to have “mitochondrial diabetes.” After obtaining informed consent from the patient, mutation of the mitochondrial gene was analyzed. In leukocytes, A→G transition at the nucleotide pair 3243 of the mitochondrial gene was detected. Although he had no cardiac symptoms, to rule out cardiac involvement, further investigations (i.e., electrocardiography, chest X-ray, and echocardiography) were performed. No abnormal findings …

BACKGROUND: The adenosine diphosphate (ADP) receptor P2Y12 plays a central role in platelet function, and this receptor is therapeutic target for thrombotic disorders. Previously, the P2Y12 gene was reported to have genetic polymorphisms, H1H2 haplotype (C139T, T744C, insertion 801A, and G52T) and C34T. The effect of these polymorphisms on the risk for arterial thrombosis, however, remains controversial. In this study, we screened the sequence variations in the P2Y12 gene, and performed case-control study to investigate the association between P2Y12 polymorphisms and coronary artery disease (CAD). METHODS AND RESULTS: Written informed consent was obtained from all study subjects who were Japanese males. Screening of polymorphisms in the P2Y12 gene comprising exon1, exon2, and intron1 was analyzed in 20 control subjects. As a result, new haplotypes were defined: haplotype A: 145C, 139C, 744T, and 1210T, haplotype B: 145T, 139T, 744C, insertion 801A, and 1210C. The G52T and C34T polymorphism were not linked with this haplotype. We next analyzed the relationship between these P2Y12 polymorphisms and susceptibility of CAD in a case-control study. One hundred and two patients with CAD were recruited at Keio University Hospital with a diagnosis of myocardial infarction or angina pectoris. CAD patients whose coronary lesions were confirmed by coronary angiography (identified stenosis ≥50%) were eligible for this study. To match CAD patients for sex and age at diagnosis of CAD, 257 healthy control subjects were recruited at their regular checkups. They had no clinical or laboratory evidence of past vascular disorders. Genotypes of the AB, C34T, and G52T polymorphisms were determined by single nucleotide primer extension-based method. We observed that the genotype frequencies of the AB (AA vs AB+BB), C34T (CC vs CT+TT), and G52T (GG vs GT+TT) did not differ between the CAD and control groups (p= 0.0635 for AB, p=0.2090 for C34T, and p=0.0816 for G52T). When study subjects were divided into the combination of two homozygous carriers (genotype combination), the AA and 34CC genotypes, and other genotypes (others), the frequency of genotype combination in CAD patients was significantly higher than that in controls (p=0.0058). Moreover, association of the genotype combination with the prevalence of CAD, adjusted for other risk factors (body mass index, smoking, hypertension, hyperlipidemia, and diabetes mellitus), was analyzed by a multiple logistic regression model, and adjusted odds ratio was 2.0 (95% CI, 1.1–3.5, p=0.0147) for the relation between CAD and the genotype combination. CONCLUSIONS: The combination of AA haplotype and 34CC genotype is highly associated with the risk of CAD. The present data point out the importance of genotypic combination, but not single specific polymorphism, to examine the association between CAD and P2Y12 polymorphisms.

Acute pulmonary edema (APE) has a poor prognosis in the general population. Mortality associated with APE in patients with end-stage renal disease (ESRD) is especially high, although specific predictors are not well understood. This study aimed to determine the potential predictive factors of outcome in patients with ESRD presenting with APE. Sixty-eight patients with ESRD (mean age, 68.9 ± 9.9 years; males, 66.2%; median duration of maintenance hemodialysis, 55.5 months) presenting with APE to a single tertiary medical center were retrospectively evaluated. The effects of patients’ characteristics, cardiovascular risk factors, variables at hospital presentation, and clinical presentation patterns on all-cause mortality were evaluated. Throughout the observational period (median follow-up period, 575 days; range, 10–2546 days), 32 (47%) patients died. In univariate analysis, older age, diabetes mellitus, peripheral artery or aortic disease, hypotension, atrial fibrillation rhythm, anemia, and hypoalbuminemia were associated with higher mortality, whereas hospital presentation from midnight to 8 am was associated with lower mortality. In multivariate analysis, age (hazard ratio (HR) = 1.05, 95% confidential interval (CI) 1.01–1.09, p = 0.018), presence of peripheral artery or aortic disease (HR = 3.36, 95% CI 1.52–7.42, p = 0.003), time of presentation from midnight to 8 am (HR = 0.40, 95% CI 0.15–0.99, p = 0.047), and atrial fibrillation rhythm at presentation (HR = 3.12, 95% CI 1.04–9.13, p = 0.044) were significantly independently associated with mortality. Our findings indicate important predictive roles of the clinical presentation pattern specific to ESRD patients, as well as their characteristics, including cardiovascular risk factors.