The ATP-sensitive K⁺ channels (K₊) are characterized by strong inhibition by intracellular ATP but their activity is also modulated by various intra- and extracellular factors with complicated and undefined mechanism. These factors include a low concentration of ADP (or ATP/ADP ratio), a mildly low pH, G-protein coupled process, adenosine and so on. Intracellular ATP has a ligand action to inhibit the channel activity on the one hand, but on the other ATP is necessary for maintaining the channels in an operative state, probably due to the enzymatic process involving ATP hydrolysis. K₊ is inhibited by antidiabetic sulfonylureas and sodium 5-hydroxydecanoate. The channels are activated by the K⁺ channel openers in an ATP-dependent manner, but may have diverse mechanisms of actions depending on different compounds. The K₊ channel openings are responsible for shortening the action potential duration (APD) and partial K⁺-efflux during early ischemia. The discrepancy between the high sensitivity of intracellular ATP to inhibit K₊ in cell-free, inside-out patches and millimolar orders of myocardial ATP concentration determined by the biochemical techniques may cast some doubts on the actual openings of this channel. It can be explained by the presence of cofactors to stimulate channel opening, heterogeneity or compartmentation of ATP distribution in the cell, the properties and high density of K₊, or a combination of these factors. The opening of K₊ during ischemia may contribute to the development and aggravation of serious arrhythmias to some extent, but their opening also protects cellular damage, limits infarct size and improves recovery of cardiac function during reperfusion, acting as a cardioprotection mechanism. K₊ opening may mimick the effects of ischemic preconditioning, but its effect may be variable among different animal species and experimental conditions. Further studies are necessary to clarify the actual role of channel opening and the molecular mechanism.

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Congestive heart failure (CHF) patients share several similar features, such as reduced cardiac contractility and neurohumoral activation to compensate the impaired cardiac function. In CHF patients, the cardiac reninangitensin (RA) system, receptors, GTP-binding proteins, and their effector molecules are inevitably exposed to chronically elevated neurohumoral stimula-tion. A widely recognized concept is that a chronic increase in such stimulation can desensitize target cell receptors and the post-receptor signal transducing pathway. Recently, reports of several studies have indicated that the inhibitory GTP-binding protein (Gi) can be increased in CHF patients and animal models. Although direct evidence for a change in catalytic protein of adenylyl cyclase has not been found, limited information has suggested a reduced catalytic activity in terminally failing hearts. In this paper, we have assessed the changesin βAR, GTP-binding protein, catalytic protein and βARK.
We also examined angiotensinogen mRNA expression in failing heart. It was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Immunohistochemical studies revealed a stronger reaction in the endocardial layer of the human left ventricle than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. Our experiments revealed a widespread immunopositive reaction for angiotensinogen in the left ventricle of diseased hearts. In the non-diseased heart, ACE and AT1 receptor RNA are present in ventricular muscles. Renin and Ao mRNA could not be detected in the subendocardium of non-diseased left ventricle, but both were present in the left ventricle of diseased hearts. These data indicate that the cardiac RA system plays an important role in the deterioration of cardiac function.

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To compare the value of exercise electrocardiography with dobutamine stress echocardiography and exercise technetium-99m isonitrile single-photon emission computed tomography for coronary artery disease, 70 patients with either suspected or proven coronary artery disease underwent dobutamine stress echocardiography, exercise technetium-99m isonitrile single-photon emission computed tomography (mibi-SPECT) and treadmill exercise electrocardiography (ECG). Dobutamine echocardiography and exercise mibiSPECT revealed a higher overall sensitivitiy than exercise testing (90 vs 57%, p0.001; 96 vs 57%, p0.001, respectively). Dobutamine stress echocardiography showed a higher specificity than both exercise mibi-SPECT and treadmill exercise electrocardiography (90 vs 71%, p>0.05; 90 and 62% p0.05, respectively) but the difference between dobutamine stress echocardiography and exercise mibi-SPECT was not statistically significant. Diagnostic accuracy of dobutamine stress echocardiography and exercise mibi-SPECT was higher than that of exercise testing (90 vs 59%, p0.001; 89 vs 59%, p0.001, re-spectively).
Dobutamine stress echocardiography and exercise mibi-SPECT have superiority over exercise testing in the diagnosis of coronary artery disease and dobutamine stress echocardiography is an alternative for exercise mibi-SPECT.

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We explored the relationship between body surface recovery time (RT), the interval between the QRS onset and the time of maximum derivative in the T-wave on a 16 precordial lead system electrocardiogram (ECG), and monophasic action potential (MAP) duration of the left ventricular endocardium in 9 patients in whom electrophysiologic testing was indicated. The usefulness of RT measurement on body surface ECG for the detection of coronary artery disease was evaluated in 98 patients who had chest pain. The RT located in the right clavicular or upper sternal area showed a very high positive correlation (r=0.91, p<0.001) with MAP duration from the left ventricular endocardium and showed specific shortening in patients with one-vessel disease of the left anterior descending coronary artery. With a criterion of the RT located in the right clavicular or upper sternal area corrected by Bazett's formula<380msec^1/2, a sensitivity of 81% and a specificity of 80% were achieved for detection of one-vessel disease of the left anterior descending coronary artery.

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The ventricular gradient vector was determined in normal persons and in cases with left and right bundle branch block (BBB) by means of the best fit method from body surface potential mapping data. Similar measurements were also made in cases with artificial ventricular pacing and the G vector during sinus rhythm was compared with that of the paced beats. Results indicated that the magnitude of the G vector in cases with BBB was smaller than in normal persons. The directional change in the G vector was found to be along the direction of the QRS change in the majority of cases with left BBB. In right BBB, the direction of the G change was variable but the angle between the QRS change was less than 90 degrees on average. Following right ventricular pacing a small increase of the G magnitude was observed acutely, which was opposite in direction to the QRS change. Possible mechanisms are discussed. The G changes in left and right BBB are considered to be based on certain chronic processes, different from those involved in the acute immediate effect of altered activation.

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In reentrant ventricular tachycardia (VT), the postpaced return cycle (RC) during transient entrainment at a pacing site far from the central common pathway is longer than the VT cycle length (VTCL), when VT is represented by a figure-eight model. However, the reentrant circuit has not been fully elucidated.
The purpose of this study was to present VT in which the postpaced RC became identical to VTCL during transient entrainment while fusion is evident in the surface electrocardiogram (ECG).
Among 38 patients with inducible reentrant VTs who underwent electrophysiologic study (EPS), 10VTs of six patients were selected. All patients had underlying heart diseases: dilated cardiomyopathy (n=2), coronary artery disease (n=1), postoperative tetralogy of Fallot (TOF; n=2), and arrhythmogenic right ventricular dysplasia (n=1). Catheter mapping was performed to demonstrate that the site of origin was distant from the pacing site.
The cycle length of induced VT (n=10VTs) was 380±41msec. Five patients (83%) had two morphological VTs; one a left bundle branch block (LBBB) and the other a right bundle branch block (RBBB) pattern. During rapid pacing, constant fusion was observed in all VTs, but the postpaced RC was identical to VTCL. In 2 patients (4VTs), the revolution of wavefronts around an anatomical obstacle (scar of myotomy in TOF, and infarction) was demonstrated.
The fact that the postpaced RC was identical to VTCL but showed fusion in the surface ECG can be explained by macro-reentry. The pacing site must be located at the preferential route of the macroreentrant circuit.

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We retrospectively studied the clinical efficacy and safety of oral flecainide in 38 patients with symptomatic arrhythmias. Patients received 100 to 200mg daily of flecainide for a mean of 25 months (range 8 to 50 months). All patients had normal cardiac function. Paroxysmal atrial fibrillation (PAF) was observed in 29 patients (76%). Other forms of arrhythmia included paroxysmal atrial flutter, seen in 3 patients (8%); premature atrial contraction and ventricular premature contraction, each seen in 2 patients (5%); and supraventricular tachycardia and ventricular tachycardia, each seen in 1 patient (3%).
A complete response was obtained in 15 (52%) of 29 patients with PAF and a partial response in 8 patients (27%). The remaining 6 patients (21%) showed no response. A complete response was also obtained in 7 of 9 patients with other forms of arrhythmia. There were no differences in cardiac function and ECG parameters before and after treatment. Flecainide was withdrawn in 4 patients due to the development of electrocardiographic abnormalities. Three of these patients showed an atrial proarrhythmic effect. Abnormal ST elevations in the precordial leads were observed in 1 patient who received 200mg of flecainide daily.
In conclusion, flecainide was effective treatment for supraventricular and ventricular arrhythmias, but attention must be paid to the drug's potential proarrhythmic adverse effects.

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Non-anemic macrocytosis is occasionally observed in patients with a history of alcoholism or chronic liver disease. Recently we reported that patients with atrial fibrillation (AF) had larger erythrocytes than normal subjects. In the present study, we examined the temporal changes in hematologic measurements during the development of AF in 88 male patients (chronic AF: 49, paroxysmal AF: 39), and compared alcohol intake among the groups. The mean corpuscular volume of erythrocytes was significantly greater in chronic AF patients, both before (98.1±6.1 (SD) fl p<0.05) and after onset (within 6 months: 98.4±7.1 fl p<0.05; 1 year: 98.6±6.2 fl p<0.01), compared with 300 age-matched male control subjects with sinus rhythm (95.9±3.6 fl). Hematocrit increased significantly with development of AF in both chronic and paroxysmal AF patients (p<0.005). Mean daily alcohol consumption did not differ significantly among the control, chronic AF and paroxysmal AF groups. Our findings indicate that erythrocyte size is already larger in patients with chronic AF before the condition develops.

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This study assessed the accuracy of indirect blood pressure (BP) measurements by simultaneously performing three kinds of indirect BP measurement on the left arm (auscultatory, microphone and oscillometric methods) and a direct BP measurement on the left arm. The subjects were 34 hospitalized patients, ranging in age from 18 to 73 years (average 47.5 years). Highly significant correlations in systolic or diastolic BP between a given pair of the three indirect methods. The indirect methods underestimated systolic BP and overes-timated diastolic BP compared with the direct method, with differences of -12.2±10.5/+4.6±7.6 (systolic/diastolic BP) with the oscillometric method, -8.1±9.7/+1.2±8.9 with the microphone method and -10.6±8.1/+3.7±6.5mmHg with the auscultatory method. The difference in systolic BP between the auscultatory and direct methods was greater and the difference in diastolic BP was smaller in subjects older than 50 years than in those aged 50 years or less ( p<0.001 for systolic BP, p<0.05 for diastolic BP). The auscultatory method revealed greater systolic BP in subjects with increased carotid arterial wall stiffness assessed by echoarteriography. Thus, it is concluded that there are inherent differences in BP between the indirect and direct methods which can be attributed to the changes in arterial wall physical properties partly due to aging.

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The aim of this study is to define the effect of sublingually administered nitroglycerin (NTG) on the diameters of the forearm arteries and veins as well as to define the relationship between these vascular changes and the forearm circumference in healthy volunteers. For this purpose, we employed a noninvasive method permitting the simultaneous quantitative recording of vascular diameters, forearm circumference and blood pressure using a miniature load cell, linear differential transformers and mercury-in-rubber strain gauge. Sublingually administered NTG (0.3mg) increased the radial arterial diameter and the forearm circumference, whereas the cephalic vein capacitance was decreased; consequently, the cephalic vein acts to moderate the increase in forearm circumference. The results clearly indicate that nitroglycerin dilates forearm arteries but not forearm veins in the normal state.

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In humans, the isthmus in the low right atrium between the tricuspid annulus and the inferior vena cava or the coronary sinus ostium is a wellestablished target of catheter ablation of common atrial flutter. In the canine model of atrial flutter with a Y-shaped incision, the tricuspid annulus was thought to constitute the essential reentrant pathway. The present study was designed to determine whether the supravalvular tissue around the tricuspid annulus is essential to atrial flutter in the canine model with an intercaval obstacle on the basis of the results of radiofrequency ablation. Epicardial approach of radiofrequency ablation was tested in 4 groups of dogs. Group A (5 dogs): Single application of radiofrequency energy (20W) for 5sec to the mid right atrial free wall. Group B (9 dogs): One to two applications to the tricuspid annulus. A ligature was also placed encircling the tricuspid annulus from the supravalvular atrial tissue to the subvalvular ventricular tissue. Group C (9 dogs): Linear transverse applications to the mid right atrial free wall between the tricuspid annulus and the intercaval obstacle. Group D (10 dogs): The isthmus between the inferior vena cava and the tricuspid annulus was ablated. After the experiment, the heart was excised for anatomical and histological studies. Atrial flutter was never abolished in all dogs in Groups A and B. A ligature encircling the tricuspid annulus also failed to terminate atrial flutter in 2 dogs tested. In contrast, atrial flutter was successfully abolished in 6 dogs (67%) of Group C and in 7 dogs (70%) of Group D. Total energy delivered was significantly higher in Group C than in Group D (364±133 versus 139±65 joules, p<0.003). The total energy required for successful ablation was related to the cross sectional area of the ablation site (r=0.55, p<0.05). These results indicate that the tricuspid annulus is not an essential part of the reentrant pathway in the canine model of atrial flutter with an intercaval obstacle. The entire atrial tissue between the anatomical barriers could be involved in the reentrant pathway, and should therefore be ablated transmurally for successful ablation.

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Norepinephrine (NE) (2.5μg/kg/min) was administered to 5-week-old male Sprague Dawley rats by subcutaneous osmotic mini pumps for 14 days to generate an in vivo cardiac hypertrophy model and the responses with respect to aging examined. In the model, ventricles were significantly hypertrophied without myocardial necrosis and without significant increases in heart rate or blood pressure; the beta adrenergic system was down-regulated. In 37-week-old rats receiving 1.0μg/kg/min NE, there was a tendency towards heart failure, and myocardial necrosis and interstitial fibrosis were revealed by histological examinations. The density of beta adrenergic receptors and adenylyl cyclase activity was lower in the older rats. The excess stimulation of adrenergic receptors caused severe cardiac injury in old rats regardless of down regulation of beta adrenergic receptors.

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To evaluate the relationship between cardiovascular injury and the pathological significance of endothelial constitutive nitric oxide synthase (ecNOS) and inducible nitric oxide synthase (iNOS) in endotoxic shock, Wistar rats were injected intraperitoneally with 10mg/kg Escherichia coli endotoxin and the resulting cardiovascular changes observed using immunohistochemistry, immunoelectron microscopy, the reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization at 4, 6, 8 and 10h after endotoxin administration. Immunohistochemical and electron microscopic observations showed that ecNOS was localized in the cytoplasmic vesicles and rough endoplasmic reticulum of the endothelium of coronary arteries and intermyocardial capillaries in both control and endotoxin-treated rats. iNOS was localized in the cytoplasmic vesicles and endoplasmic reticulum of vascular endothelial cells, vascular smooth muscle cells and cardiomyocytes after endotoxin administration. The RT-PCR study confirmed the expression of ecNOS and iNOS mRNA in the heart tissues of all animals including controls. In situ hybridiza-tion showed that ecNOS mRNA was expressed in the cytoplasm of vascular endothelial cells in control and endotoxintreated rats. After endotoxin administration, iNOS mRNA was strongly expressed in vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes and a small number of macroph-ages. Bacterial lipopoly-saccharide induces rapid release of nitric oxide in the microvasculature and cardiomyocytes resulting in the depression of cardiomyocyte contraction. These findings may describe the cardiac response after endotoxin treatment.

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Three cases of cardiac papillary fibroelastomas are described. Two-dimensional echocardiography detected the tumors in the mitral valve, the cordae tendinae and in the apex of the left ventricle-a unique location. The tumor excisions were combined with bypass operation, mitral valve reconstruction, repair of cordae tendinae and Maze-procedure. The three patients are doing well after surgery.

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