The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.

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Our objective was to clarify the management of patients with silent myocardial ischemia (SMI) and documented coronary artery disease. We evaluated 222 such patients who did not develop anginal pain during exercise thallium-201 imaging (ST-TL). They were divided into low- and high-risk groups based on results of left ventriculographic findings at rest, ST-TL, and coronary angiography. The incidence of cardiac events was 28/222 (13%) overall, being 9 of 110 (8%) in the low-risk patients, and 19 of 112 (17%) in the high-risk group. Kaplan-Meier survival analysis revealed a significant difference between the two groups (p=0.020). Analysis of the survival of the high-risk group revealed significant differences between the patients with a negative and positive redistribution (p=0.047), but such differences were not significant in the low-risk patients. Therefore, the classification of SMI patients into low- and high-risk categories was an appropriate strategy. ST-TL was useful for identifying patients with myocardial ischemia and selecting those to receive coronary revascularization and/or drug therapy.

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MRI of subjects with silent intracranial damages may provide more evidence than CT. Our objectives were to determine the prevalence of silent MRI lesions in patients with coronary artery disease. The study included 72 consecutive patients with angiographically proven coronary artery disease and 26 age and sex matched controls with normal coronary angiography. All subjects were evaluated for coronary atherosclerosis (Gensini and coronary angiography scores), the number of silent cerebral lesions detected by MRI, carotid stenosis and the risk factors for stroke. Thirty one of 72 (43.0%) patients had silent brain lesions on MRI while 8 of 26 (30.7%) control subjects showed silent brain infarction. The main finding on T₂-weighted MRI was white matter hyperintensities (WMH) which were seen in all patients with silent brain lesions. The mean age of the patients with coronary artery disease and with silent cerebral lesions was significantly higher than that of patients without silent brain lesions. The Gensini score, coronary angiography score and prevalence of carotid stenosis are significantly higher in patients with silent cerebral lesions than that of patients without silent cerebral lesions. There was no significant difference between silent cerebral lesions and the other risk factors for stroke.
Silent brain lesions are a common complication in patients with coronary artery disease. In patients with coronary artery disease, carotid artery stenosis and age were important risk factors for the development of silent brain infarction.

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This study was undertaken to determine whether dl-sotalol can prevent ventricular tachyarrhythmia inducibility that can be predicted from electrophysiologic parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic studies before and after dl-sotalol (320mg/day).
In 9 of 16 patients (56%) after dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire stimulation protocol (responders).
There were significant differences in QT interval (462±52 vs. 415±34 msec; p<0.05) and ventricular effective refractory period (VERP) at 600, 400 and 300 msec (302±28 vs. 262±20 msec; p<0.001, 280±23 vs. 240±21 msec; p<0.001, 256±24 vs. 222±12 msec; p<0.005, respectively) between responders and non-responders. The percentile increases in VERP (%VERP) at 600, 400, and 300 msec in responders were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%, respectively.
Isoproterenol administered to responders did not fully reverse the dl-sotalol-induced prolongation of VERP (ΔVERP) at 600, 400, and 300 msec, which remained significantly prolonged compared to the baseline (281±18 vs. 241±16 msec; p<0.01, 258±20 vs. 223±21 msec; p<0.01, 247±22 vs. 202±16 msec; p<0.01, respectively). %VERP did not exhibit significant differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a reverse use-dependency.
The results suggest that ΔVERP in responders did not show reverse use-dependency, and that the phenomenon may account for the efficacy of dl-sotalol.

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Atrial reentrant tachycardia (ART) was ablated in an anatomically guided approach. Five patients with ART underwent 2 linear incisions without careful pace or activation mapping. One line was from an atrial activation site earlier than P wave onset to the nearest fixed anatomic conduction barrier, i. e., the inferior vena cava or coronary sinus ostium. The other line was made just above or closely crossed the first line vertically. Mean application time was 29±19 minutes, and the application energy was 14, 001±12, 322 joules. Mean follow-up after ablation was 15±10 months. Three patients underwent elecrophysiologic study three months after and sustained ART was not induced. All patients were free of sustained tachycardia events without antiarrhythmic drugs during the postoperative clinical course. Although anatomically guided ablation for ART requires much time and energy, it is easily and effectively done without careful activation or pace mapping, and is indicated if ablation using activation mapping or entrainment technique fails to cure the ART.

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Increased mortality in digoxin-treated subjects has been demonstrated in patients with recent myocardial infarction. Those with congestive heart failure (CHF) due to causes other than myocardial infarction seem to be free from this effect. No information is currently available concerning mortality in elderly people who are frequently prescribed digitalis even in the absence of CHF. The aim of this study was to investigate whether subjects improperly receiving digoxin were worse off than those not receiving this drug.
This analysis is a part of CASTEL, a population-based prospective study that has enrolled a cohort of 2, 254 subjects aged ≥65 years. CHF was diagnosed in 187 subjects and atrial fibrillation (AF) in 90. The remaining 1, 977 were free from CHF and in sinus rhythm, but 447 were treated with digitalis. Cumulative mortality and morbid events by digitalis treatment were calculated in all these categories.
Among subjects free from CHF and AF (improper use), all-cause and cardiovascular mortality was significantly higher among those taking digitalis than in those who did not. Non-fatal events including CHF were also more apparent in the former than in the latter. Cox analysis confirmed digitalis as a predictor of mortality in these subjects. No effect of digitalis on survival was found in patients with CHF or AF (proper use).
In elderly subjects without atrial fibrillation or CHF, the use of digitalis worsens morbidity and mortality.

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The purpose of this study was to clarify the presence of isovolumic relaxation flow in patients with left bundle branch block and normal coronary arteriogram. Twenty-four patients with left bundle branch block and normal coronary arteriogram were examined by pulsed Doppler echocardiography and were compared with 20 age- and gender-matched healthy subjects. Impaired left ventricular relaxation was found in patients with LBBB. All 24 study patients showed isovolumic relaxation flow, but only 4 healthy subjects had isovolumic relaxation flow (p<0.05). Peak velocity of the isovolumic relaxation flow ranged from 20-42cm/s. In the study group, left ventricular systolic function was normal in 17 patients, and reduced in the remaining patients. At the end of this study, the presence of isovolumic relaxation flow which may be due to an abnormal septal motion was found in patients with left bundle branch block and normal coronary arteriogram.

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Eight patients, 9.1 to 16.5 years of age, were studied 2.8 to 8.5 years after Fontan operation. Oxygen utilization was determined during upright bicycle exercise. The cardiac index and stroke index were measured by echocardiography and the anaerobic threshold was determined. The results were compared with 10 patients after surgical closure of the atrial septal defect. Anaerobic threshold (AT) in Fontan patients was lower than in the control subjects. Oxygen consumption at each stage of exercise was significantly lower in the Fontan group compared with the control subjects. From the beginning of exercise until AT, the increase in stroke index was lower in the Fontan patients than in the control subjects. After that point, the stroke index decreased significantly in the Fontan patients while it remained almost at the same level in the control subjects. Significant correlations were observed between the oxygen pulses and the stroke index at AT both in the control and Fontan groups. These results suggest that impaired exercise capacity in Fontan patients is mainly due to a subnormal response of the stroke index at AT and to the decreased response of the stroke index and the heart rate at the maximal workload.

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The aim of the study was to investigate the developmental pattern of hypoplastic pulmonary artery (p. a.) bed augmented by systemic-to-pulmonary shunt in children with univentricular heart scheduled for Fontan surgery.
For the study, a highly selected patient cohort was chosen (12 patients aged between 5 and 19 years; mean 9.5 years) with comparable initial morphological conditions of univentricular heart and hypoplastic p. a. bed, who after mandatory systemic-to-pulmonary shunt underwent Fontan procedure at time of normalization of pulmonary artery size. Further selection criteria were: normal pulmonary vascular resistance at time of Fontan procedure, competent av valve (s), and globally unimpaired ventricular function.
All patients were grouped according to the preoperative pulmonary flow index (Qpi; L/min/m² b. s. a.) measured immediately before Fontan operation: Group A: 1.5-2.5; B: 3.0-4.0; C: 4.0-5.0; D:>6.0, and their cardio-pulmonary hemodynamic situation (Hb, SAsat%, Qp/Qs, PAP, Rp/Rs, EDVP, FS%, ventricular diastolic compliance (VC=EDVP/Qpi+Qsi) as well as the pulmonary artery size and area using standard (Nakata-index, McGoon-ratio) and a self designed computer assisted planimetric area calculation (PPAAI; cm²/m² b. s. a.) analysed.
Each patient underwent 1-3 shunt procedures, the mean shunt patency period for groups A, B, C and D was 12, 8.6, 5.3, and 4.5 years, respectively. The mean Nakata-index (283, 297, 324, 405 in groups A-D) and the McGoon-ratio (2.0, 2.2, 2.8, 3.3 in groups A-D) correlated with the Qp index, reflecting flow dependent development of pulmonary artery bed. No correlation was found between Qpi and PPAAI (47, 40, 41 and 47 in group A-D). The VC/Qp relation showed an inversely proportional pattern with values 2.3, 1.0, 0.8, 0.7 for corresponding groups A-D, the lowest VC in group A correlated with polygloulic status (Hb-values; g/dl): 21.3 in A vs 19.8, 18.0 and 16.5 in B-D) and mean arterial SAsat-values (77% in A vs 83%, 84% and 89% in B-D).
In conclusinon, in our highly selected patient cohort, the development of p. a. size was strongly flow-dependent, and patients with restrictive pulmonary flow neede an approximately threefold longer time period to normalize their p. a. size compared to those with excessive flow. In patients with retrictive pulmonary flow, the Nakata-index underestimated the degree of development of the pulmonary artery system, probably due to the distortion of the proximal p. a. segment.In consequence, in these patients the normalization of the, p. a. bed and thus suitability for the Fontan procedure probably occurred much earlier. Besed on our observatious and those of others, in patients with excessive flow the normalization of p. a. bed, provided it occurs within 3-4 years, seems not necessarily to be associated with a deterioration of ventricular function.

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Plasma lipid and lipoprotein levels reflect in part the influence of relevant genetic loci. Defects at some of these loci account for specific types of dyslipoproteinemia occurring with regularity among family members. In the course of familial investigations of coronary artery disease, we identified an family in which several members were affected with elevated low density lipoprotein (LDL) cholesterol levels. To study the genetic defects responsible for plasma lipoprotein abnormality in this pedigree, we developed a simple method for genotyping a single base substitution that does not affect a restriction recognition enzyme site in exon 10 of the LDL receptor gene. Using our mismatched PCR method, this G- >A substitution at nucleotide 1413 could be genotyped in the form of a biallelic restriction fragment length polymorphism (RFLP) after digestion with restriction enzyme Hpa II. Linkage analysis using this molecular method demonstrated that the defect at the LDL receptor locus is responsible for elevated LDL cholesterol phenotype observed in this family by segregation of defective alleles at the LDL receptor locus with the disease (peak decimal logarithm of odds score >3.0).

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Susceptibility to reentrant tachyarrhythmias and the antiarrhythmic efficacy of class III agents are related more to the duration of the refractory period (ERP) than to the repolarization time (RT). We measured both ERP and RT in a canine model of healing myocardial infarction, and evaluated the effect of a class III agent (E4031) on these parameters and on the inducibility of ventricular tachyarrhythmias. ERP and RT on the unipolar electrogram were measured at several cycle lengths in the normal (NZ) and infarct zones (IZ), respectively, in 10 canine myocardial infarction models and extrastimulation was used to induce ventricular arrhythmias. Measurements were repeated after E4031 administration.
At baseline, both ERP and RT were significantly longer in IZ than in NZ with ERP/RT ratio also higher in IZ. This ratio tended to increase at longer cycle lengths. E4031 increased ERP and RT both in NZ and IZ at all cycle lengths, but increased the ERP/RT ratio predominantly in IZ. E4031 prevented induction of sustained VT or VF, which was inducible in 3 out of 10 dogs at baseline, although it facilitated induction of VF in 1 dog with no baseline arrhythmia. By increasing the ERP/RT ratio, class III drugs may shorten the relative refractory period in IZ at the expense of a greater ERP difference created between NZ and IZ.

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The effects of the angiotensin converting enzyme (ACE) blocker temocapril on the capillary network of the left ventricle were studied in strokeprone spontaneously hypertensive rats (SHRSP). The ACE blocker was dissolved in the drinking water and supplied to 24 and 32 week old SHRSP ad libitum for 5 weeks. The capillaries of the wall of the left ventricle were studied using a double staining method to differentiate the arteriolar, intermediate and venular capillary portions. Capillary density increased and capillary domain areas decreased in all capillary portions compared with untreated control SHRSP in both age groups. The proportion of venular capillary portions was increased by temocapril treatment. The results indicate that the late start of ACE blockade caused the regression of the hypertrophied cardiomyocytes, which is characteristic of SHRSP, and the rearrangement of capillary portions. The plasma concentration of angiotensin II was significantly lower in temocapril-treated SHRSP compared to the control group. The implication is that intrinsic angiotensin II exerts an appreciable effect on the function, structure and capillary network in the left ventricular wall in SHRSP.

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