Background A link between venous thromboembolism (VTE) and air travel has been recently discussed, so the present study aimed to clarify the characteristics of acute pulmonary thromboembolism (PTE) associated with air travel in Japan. Methods and Results The study group comprised 36 patients with acute PTE associated with air travel. Patients' characteristics, clinical risk factors for VTE and coagulation abnormalities were investigated, and compared with a group of PTE not associated with travel. Of the 36 cases, 30 cases were female, 34 were over 40 years of age and all had flown more than 6 h. Two-thirds of all cases did not leave their seats during the flight. Of the patients, 44% had no clinical risk factors for VTE or coagulation abnormalities. Idiopathic PTE (ie, PTE without clinical risk factors or coagulation abnormalities) was significantly more common in the air travel group. Conclusion Acute PTE associated with air travel in Japan is common in elderly women and may occur without any clinical risk factors for VTE or coagulation abnormalities. Remaining seated throughout the flight increases the risk. (Circ J 2005; 69: 1297 - 1301)

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Background Early defibrillation and cardiopulmonary bypass have been postulated to be a promising intervention against out-of-hospital cardiac arrest (OHCA); however, little is known about the long-term prognosis. The effects of early recovery of circulation (ROC) on neurological recovery and the long-term outcome in patients with OHCA were examined. Methods and Results Functional recovery and long-term (22.0±15.3 months) outcome were examined in 100 patients with definite diagnosis of OHCA. Spontaneous circulation recovered in 79% of the patients (using on-site counter shock in 20% of the patients). Cardiopulmonary bypass was performed in 38 of the OHCA patients. The total survival and favorable neurological recovery rates were 40% and 25%, respectively. The patients with favorable recovery obtained early ROC (28.2±16.0 min). Receiver-operating characteristic analysis showed that a period of less than 35 min for ROC was the optimal period for achieving a favorable recovery, with sensitivity of 68% and specificity of 73%. The patients with a prior history of heart failure or reduced left ventricular ejection fraction exhibited more frequent, exacerbated heart failure and ventricular arrhythmias. Conclusions Early ROC using on-site counter shock or cardiopulmonary bypass might result in better long-term outcome in patients with OHCA of cardiac origin. (Circ J 2005; 69: 1302 - 1307)

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Background Although short-acting nifedipine does not prevent myocardial infarction (MI), calcium antagonists with a long half-life may be effective. Methods and Results The present study was a retrospective analysis of the incidences of cardiac events among patients with a healed MI treated with 3 times-a-day type nifedipine (half-life 1.8 h; n=617), twice-a-day type nifedipine (half-life 4.0 h; n=527) and those not taking calcium antagonists (n=1,593) from 1986 to 1993, and the incidences of those on once-a-day type calcium antagonists (half-life 11.0 h; n=903) and those not taking calcium antagonists (n=2,788) from 1994 to 2001. Cardiac events included cardiac death and nonfatal recurrent MI. Single and multivariate analyses using the Cox-Hazard model were performed. From 1986 to 1993 cardiac events occurred in 38 patients with 3-times-a-day nifedipine (6.2%, hazard ratio and 95% confidence interval: 1.45 and 0.93-2.27), in 18 patients with twice-a-day nifedipine (3.4%: 0.68 and 0.39-1.20), 57 patients without calcium antagonists (3.6%). Cardiac events also occurred in 11 patients with once-a-day type nifedipine (1.2%: 0.72 and 0.37-1.42) and 48 patients without calcium antagonists (1.7%). Of the once-a-day type calcium antagonists, cardiac events were the lowest (2 patients, 0.6%: 0.32 and 0.08-1.31) in patients with amlodipine (half-life 39.0 h; n=334), which has the longest half-life. None of these drugs were a significant factor in the increase or decrease in the incidence of cardiac events. However, there was a good correlation between the half-life of the calcium antagonist and the hazard ratio for reducing cardiac events. Conclusion Although there was a tendency toward a reduction in cardiac events using calcium antagonists with long half-life, none of these drugs could significantly reduce the incidence of cardiac events in patients with a healed MI. (Circ J 2005; 69: 1308 - 1314)

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Background The relationship of the genotype for the angiotensin-converting enzyme (ACE) with exercise capacity or training effects has been studied in athletes or healthy persons, but recently the ACE DD genotype was reported to be associated with decreased exercise capacity in patients with congestive heart failure. Therefore, in the present study the association between the ACE genotype and exercise capacity was investigated in patients with acute myocardial infarction (AMI) participating in cardiac rehabilitation (CR) for 3 months. Methods and Results The study population comprised 168 patients stratified as II (n=75), ID (n=67), and DD (n=26) according to ACE genotype. Baseline left ventricular ejection fraction (LVEF) was similar among the genotype groups. In all patients, exercise capacity (peak work rate (PWR) and peak oxygen uptake (PVO ₂)) significantly increased after CR. However, no differences were observed in PWR and PVO₂ among the genotype groups at baseline or after CR. The results were similar even when analyzed in 60 patients with left ventricular (LV) dysfunction (LVEF <45%). Conclusion The present study suggests that there is no association between ACE I/D polymorphism and exercise capacity in patients after AMI, even with LV dysfunction. Furthermore, ACE genotype may have no influence on the effects of CR after AMI. (Circ J 2005; 69: 1315 - 1319)

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Background Sleep-disordered breathing may affect coronary artery disease, so patients treated by percutaneous transluminal coronary angioplasty were studied to investigate the relationship between nocturnal oxygen desaturation (NOD) and the loss index. Methods and Results The nocturnal oxygen desaturation index (ODI) was determined by means of a pulse oximeter in 35 patients with coronary artery disease treated by stent placement. The patients were divided into 3 groups according to ODI: <5 events/h (group N, n=6), between 5 and 14 events/h (group A, n=19), and ≥15 events/h (group B, n=10). The relationship between the ODI and loss index was examined in each group. The loss index, 0.27±0.23 in group N, 0.30±0.27 in group A, and 0.70±0.32 in group B, differed significantly between groups N and B (p=0.007). In all patients, the loss index showed a significant positive correlation with the ODI (R=0.585, p=0.002). Conclusions These findings suggest that NOD may be an important contributor to coronary restenosis in patients treated with stent placement. (Circ J 2005; 69: 1320 - 1326)

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Background An inverse relationship between surgeon volume or hospital volume and mortality has been reported in Western countries, but seldom in Asia. Methods and Results The data of 4,724 patients with coronary artery disease who underwent coronary artery bypass graft (CABG) surgery in Taiwan between 1^st January 2000 and 31^st December 2001 were analyzed in this prospective cohort study. Overall, 3.45% of patients died in-hospital (IH), and 6.48% patients died within 30 days after discharge (AD30); 85.0% of patients in the AD30 group died at home within 1 day of discharge because of a "cultural preference for dying at home". After adjustment by stepwise logistic regression for age, sex, cardiac function, co-morbidity and in-hospital complications, higher provider volume was still associated with lower mortality rates for CABG, especially higher surgeon volume. Because IH mortality can be affected by different culture, the IH plus AD30 mortality rate is more appropriate as a proxy to reflect the mortality of a specific procedure. Conclusions The relationship of higher-volume hospitals or surgeons with lower mortality rate for patients undergoing CABG is a general phenomenon in Western and Chinese societies. However, the combination of the AD30 and IH mortality rates has to be considered when investigating procedural mortality rates in Chinese society. (Circ J 2005; 69: 1327 - 1332)

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Background Because there are no guidelines concerning coronary spasm in Japan, the present study examined the current status of the spasm provocation test. Methods and Results Questionnaires concerning the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests over 3 years (2001-2003) and the status of spasm provocation tests were sent to members of the Japanese Circulation Society in 120 cardiology hospitals in the Chugoku and Shikoku areas. Completed surveys were returned from 45 hospitals, giving a collection rate of 38%. As a spasm provocation agent, acetylcholine tests were performed in 29 hospitals, and ergonovine tests in 18 hospitals. Non-invasive spasm provocation tests were performed in only 9 hospitals (20%). In total, 5,267 patients underwent acetylcholine spasm provocation test (2,387 patients) or ergonovine spasm provocation test (2,880 patients) and vasospastic angina was diagnosed in 1,663 (2.4%) patients. Invasive spasm provocation tests were performed in 7.8% of patients with diagnostic catheterization and the spasm-positive rate was 31.6%. The difference among hospitals concerning the number of invasive spasm provocation tests was remarkable, and the angiographic spasm-positive standard and acetylcholine/ergonovine dose varied among the hospitals. Conclusions Guidelines on coronary spasm in Japan are essential to overcome the current differences between institutions. (Circ J 2005; 69: 1333 - 1337)

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Background Exercise gated single-photon emission computed tomography (SPECT) using technetium-99m (^99mTc)-sestamibi evaluates both myocardial perfusion during stress and wall motion >30 min after the stress, which has the potential to assess not only exercise-induced myocardial ischemia but also the development of myocardial stunning. Methods and Results To evaluate the incidence of post-stress myocardial stunning, as well as comparing the effects of different stress methods on the development of stunning, 179 consecutive patients with known or suspected coronary artery disease (CAD) underwent ^99mTc-sestamibi SPECT with either exercise (n=135) or adenosine triphosphate disodium (ATP) (n=44). Electrocardiogram-gated SPECT images were acquired >30 min after the stress and again 4 h later, and perfusion and wall motion were evaluated. Post-stress myocardial stunning occurred in 24 patients (13%): 22 after exercise and 2 after ATP stress. The magnitude of the transient wall motion abnormality after exercise was greater in patients with severe ischemia, compared with those with mild-to-moderate ischemia (p<0.0001). By contrast, with ATP stress, the magnitude of the transient wall motion abnormality was similar, regardless of the severity of perfusion abnormality. Furthermore, a significant correlation between summed difference score and transient wall motion abnormality was found after exercise (r=0.68, p<0.0001). With ATP, however, no such correlation was observed (r=0.28, p=NS). Conclusions Using ^99mTc-sestamibi gated SPECT, myocardial stunning is frequently observed after exercise and correlates with the severity of myocardial ischemia, but this does not occur with ATP, which is regarded as a specific marker for severe CAD. (Circ J 2005; 69: 1338 - 1345)

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Background Patients with acute coronary syndrome (ACS) frequently have vulnerable plaques in the remote coronary arteries, suggesting that ACS is part of the pan-coronary process. In the present study the computed tomography (CT) plaque density in non-culprit atherosclerotic coronary artery lesions was evaluated by multislice computed tomography (MSCT) in patients with ACS and non-ACS. Methods and Results MSCT was performed in 21 patients with ACS and 53 patients with non-ACS: 16 of the 21 ACS patients (76%) and 30 of the non-ACS 53 patients (57 %) had non-calcified plaques in the non-culprit coronary arteries (p=0.18). CT-low-density plaques (CT density <68 Hounsfield units (HU)) were more frequent in the ACS group (13/16 patients, 81%) than in the non-ACS group (13/30 patients, 43%, p=0.03). In addition, the CT density of the non-culprit lesion was significantly lower in patients with ACS than in those with non-ACS (44.1±22.9 and 77.3±33.7 HU, respectively). Conclusion Patients with ACS more frequently had CT-low-density plaques in the non-culprit, remote arteries than those with non-ACS, which suggests that ACS treatment should focus not only on stabilizing the culprit lesion but also on systemic stabilization of non-culprit lesions. (Circ J 2005; 69: 1346 - 1351)

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Background The most common cardiac tumors in young children are rhabdomyoma and fibroma, and prognosis depends on the tumor's characteristics. In the present study electron-beam computed tomography (EBT) was used to evaluate tumor characteristics and myocardial perfusion in 6 children with cardiac tumors. Methods and Results Five children had rhabdomyomas and 1 had a fibroma. In the precontrast study, the computed tomography numbers of rhabdomyomas were higher and those of the fibroma were slightly lower than those of the normal myocardium. In the early postcontrast study, the size, location, shape and number of the tumor were clearly detected, and in the late postcontrast study, the fibrous characteristics of the tumor were seen. The fibroma contained calcification and 2 rhabdomyomas contained a fat density spot. In the cine-mode study, both the tumor and ventricular wall motion could be simultaneously evaluated. There was a filling defect of the left ventricular myocardium on the early postcontrast scan of 1 child with a rhabdomyoma and dyskinetic wall motion at the same region in the cine-mode study. Conclusion EBT was useful for evaluating tumor characteristics in children. (Circ J 2005; 69: 1352 - 1356)

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Background A multicenter investigational survey (Japanese Guideline for Arrhythmia Management By Individual Therapy) was conducted to evaluate the validity of using CD-ROM guidelines vs physician choice for the selection of antiarrhythmic drugs. Methods and Results Patients with paroxysmal atrial fibrillation (PAF, n=274) or premature ventricular contractions (PVC, n=216) were enrolled. The rate of concordance for drug selection between the treating physician and the CD-ROM was 216 of 274 patients (78.8%) with PAF. Of these, 168 (61.3%) were concordant for first-line agents and the remaining 48 (17.5%) were concordant for second-line agents. The concordance for the treatment of PVC was 154/216 cases (71.3%). Of these, 106 (49.1%) were concordant for first-line agents and the remaining 48 (22.2%) were concordant for second-line agents. Nonconcordance for PAF therapy was more likely to occur for patients with underlying heart disease (p<0.05), depressed cardiac function (p<0.001), and with more frequent ECG abnormalities and renal dysfunction. These differences were not seen in patients with PVC. Conclusion The CD-ROM guidelines appear to be valid in the selection of antiarrhythmic drugs for both PAF and PVC, but their usefulness is influenced by the patient's clinical characteristics. (Circ J 2005; 69: 1357 - 1360)

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Background The repolarization properties of the crista terminalis (CT) cells have not been elucidated in patients with sinus node disease (SND). In the present study a new technique of recording the monophasic action potential (MAP) at the CT was used to examine the repolarization of the right atrium (RA) in SND patients. Methods and Results Symptomatic SND (n=13) patients and age-, sex-matched control patients (n=13) were tested. The MAP duration (MAPD) at a basic cycle length of 600 ms was recorded at the CT in the superior vena cava - RA junction and at the middle - anterior RA with the effective refractory period (ERP) at the high RA. In 6 controls and 4 SND patients, the effect of adenosine triphosphate on the MAPD was examined. The MAPD at the CT exceeded that at the middle - anterior RA in both groups. The MAPD at the CT in the SND group was significantly prolonged compared with the control group (CT: 358±39 ms vs 289±43 ms). Between the SND and control groups, the MAPD at the middle - anterior RA (278±36 ms vs 265±39 ms) and ERP (294±42 ms vs 266±41 ms) did not differ. Both the corrected-sinus node recovery time and sinoatrial conduction time were better correlated with the MAPD at the CT than the MAPD at the middle - anterior RA and ERP. Adenosine triphosphate shortened the MAPD, which was augmented at the CT in the SND patients. Conclusion A novel method of estimating the MAP at the CT revealed the characteristics of atrial repolarization in SND patients. (Circ J 2005; 69: 1361 - 1367)

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Background Ventricular alternans of repolarization produces serious ventricular arrhythmias in experimental models. The present study investigated the role of alternans of atrial repolarization in patients with atrial fibrillation (AF). Methods and Results Electrophysiological studies were performed in 19 patients without structural heart disease. Monophasic action potentials (MAP) were recorded with 2 Franz catheters during steady state pacing, starting at a cycle length (CL) of 400 ms with subsequent decrements of 10 ms. Duration from the onset of upstroke to 90% repolarization of the MAP were measured. If discordant alternans (DA) was present during pacing, verapamil was administrated, and MAP measurements were repeated. Rapid pacing resulted in concordant alternans to DA in 13 of 19 (68%) patients. AF was initiated after the induction of DA in 8 of 13 patients (p=0.012). Verapamil treatment resulted in a significant decrease in the longest pacing CL at which DA was induced (207±19 vs 178±17 ms, p<0.0001). Conclusions Rapid atrial pacing induced DA and was associated with initiation of AF. Furthermore, induction of DA was suppressed by verapamil. Reducing the spatiotemporal repolarization heterogeneity may be how the calcium-channel blockade prevents initiation of AF. (Circ J 2005; 69: 1368 - 1373)

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Background Left ventricular hypertrophy (LVH), as well as the geometry pattern of the left ventricle, is believed to be an independent risk factor for hypertension. The present study investigated the changes in left ventricular mass, diastolic function and geometry in hypertensive patients in a prospective 5-year follow-up in conjunction with an evaluation of the regularity and effectiveness of treatment. Methods and Results One hundred hypertensive patients older than 18 years were examined according to the study protocol, which included registration of weight, height, vital signs, and echocardiography. After 5 years a repeat examination was performed. Patients were divided into 3 groups according to blood pressure (BP) control: group 1 (n=32), no regular medication; group 2 (n=44), regular treatment but no target BP levels; group 3 (n=14), regular effective treatment. In group 1 an increase in LVH and worsening of diastolic function were observed; in group 2 LVH and isovolumetric relaxation time remained unchanged, while the early peak velocity/atrial peak velocity ratio decreased; in group 3 there was a significant decrease in LVH. The geometry pattern only changed in 21 (23%) patients. Conclusions LVH can be successfully reversed in only hypertensive with adequate BP control. The remodeling pattern appears to be a stable characteristic of the patient and transformation of one pattern into another is infrequent. (Circ J 2005; 69: 1374 - 1379)

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Background Low-renin (volume-dependent) hypertension represents 25-30% of all cases of primary hypertension. Endothelial dysfunction and vascular remodeling are associated with hypertension but their relevance to volume-dependent hypertension (VDH) is not yet known. To evaluate this, flow-mediated dilation (FMD) of the brachial artery and the carotid intima-media thickness in the distal common carotid artery were measured and compared between renin-dependent mild-hypertensive patients (RDH) and controls. Method and Results The study group comprised 40 mild-hypertensive patients and 25 controls. Plasma renin activity (PRA), plasma aldosterone concentration, angiotensin II and nitrite/nitrate plasma levels were measured. According to PRA, subjects were classified as VDH (<0.6 ng · ml ^-1 · h^-1), or RDH (>0.6 ng · ml^-1 · h ^-1). Vascular function was evaluated by FMD before and after reactive hyperemia (RH) and glyceryl-trinitrate (GTN) administration. FMD in response to RH and GTN in the VDH group when compared with RDH group was 10.2±2.8% vs 13.3±3.6% (p=0.01); and 16.0±3.5% vs 19.9±4.5% (p=0.01), respectively. Conclusion This study showed impaired FMD and reduced GTN response in mildly hypertensive patients with low-renin plasma levels. (Circ J 2005; 69: 1380 -1385)

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Background The goal of the present study was to examine the cardiac configuration and pulmonary vascular changes in patients with portopulmonary hypertension (PPHTN) and compare them with those of idiopathic pulmonary arterial hypertension (IPAH). Methods and Results The subjects were 10 patients with PPHTN and 18 with IPAH. In PPHTN, the increases in the right ventricular end-diastolic volume index (89±19 vs 128±50 ml/m²; p=0.04), right end-systolic volume index (50±19 vs 95±47 ml/m ²; p=0.02) and right ventricular mass index (47±18 g/m² vs 79±31; p=0.04) were low compared with IPAH. The decrease in the right ventricular ejection fraction was also low in PPHTN (45±10 vs 28±13%; p=0.01). The degree of sparse arborization and abrupt narrowing on wedged pulmonary angiography was moderate in PPHTN compared with IPAH. In PPHTN, the proximal pulmonary arteries were dilated near the segmental arteries, which were narrow in IPAH. Conclusion Changes in the configuration of the heart were moderate in PPHTN compared with those in IPAH. The degree of sparse arborization and abrupt narrowing were also moderate in PPHTN. (Circ J 2005; 69: 1386 - 1393)

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Background An effect of aldosterone on ventricular fibrosis has been demonstrated in animals, but remains unclear in human patients. This study aimed to investigate (1) the relationship between left ventricular (LV) fibrosis and myocardial ultrasonic texture as assessed with myocardial radio-frequency (RF) signals analyzed from the viewpoint of their waveform with chaos theory in animals and (2) serial changes in myocardial ultrasonic texture following long-term aldosterone blockade in patients with LV hypertrophy. Methods and Results In an animal study, Sprague-Dawley rats were divided into 2 groups with and without adriamycin administration, and the relationship between the RF signals and LV fibrosis was assessed. In a clinical study, effects of 12-month-administration of spironolactone were assessed in patients with LV hypertrophy. The animal study revealed that the correlation dimension (CD) calculated from the RF signals inversely correlated with the area of fibrosis. The clinical study demonstrated an increase in CD following 6-month administration of spironolactone. The changes in CD positively correlated with those in the serum carboxy-terminal telopeptide of collagen type I. Conclusion Myocardial RF signals analyzed with chaos theory reflect the severity of LV fibrosis. Aldosterone blockade may alter myocardial ultrasonic texture with regression of LV fibrosis, at least partly through enhanced collagen degradation. (Circ J 2005; 69: 1394 - 1400)

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Background The role of arginine vasopressin (AVP) in the heart has yet to be determined. The present study was designed to examine whether AVP is regulated in the human heart. Methods and Results The subjects were 93 patients who underwent coronary angiography and left ventriculography. Blood samples were collected at the aortic root (AO) and the coronary sinus (CS) to measure the plasma levels of AVP. The patients who showed increases in AVP levels at the CS and AO were assigned to the increased AVP group and those who showed no change or a decrease were assigned to the non-increased AVP group. Cardiac function was compared between these 2 groups. There was a significant difference (p<0.0234) in left ventricular end-diastolic volume index between the increased AVP group (125.5 ±53.4 ml/m²) and the non-increased AVP group (102.2±30.6 ml/m²). There was also a significant difference (p<0.0137) in left ventricular stroke volume index between the increased AVP group (66.6±23.2 ml/m²) and the non-increased AVP group (54.4±18.6 ml/m²). Conclusion These results suggest that both the production of AVP and synthesis with its receptors may be enhanced at regional sites of the human heart in the volume load. (Circ J 2005; 69: 1401 - 1404)

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Background Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca²⁺ influx through L-type Ca²⁺ channels. In this study the expression of the L-type Ca²⁺ channel α₁ subunit gene in the developing mouse heart was investigated. Methods and Results Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Ca_v1.3 mRNA was higher than that of Ca_v1.2 mRNA. With development, Ca_v1.2 mRNA increased and Ca_v1.3 mRNA decreased. Analysis of Ca_v1.3 splicing variants showed that Ca_v1.3(1b) mRNA was expressed at a higher density than Ca_v1.3(1a) mRNA. Ca_v1.3 protein was detected only at 9.5 dpc, whereas Ca_v1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca²⁺ currents were prominent at 9.5 dpc. The Ca²⁺ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca²⁺ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca²⁺ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. Conclusions The Ca_v1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity. (Circ J 2005; 69: 1405 - 1411)

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Background Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1). Sepsis-induced myocardial depression results from the expression of inducible nitric oxide synthase (iNOS) evoked by inflammatory cytokines. Methods and Results The effect of CT-1 on lipopolysaccharide (LPS)-induced cardiac dysfunction was examined in a rat model of sepsis. In the absence of CT-1, LPS (1 mg/kg ip) elicited a reduction of systolic function and dilation of the ventricular cavity within 3-6 h after administration. These physiological effects were accompanied by increased ventricular phosphorylation of signal transducers and activators of transcription (STAT) 1 and STAT3, activation of nuclear factor-κB and expression of iNOS mRNA. Notably, administration of CT-1 (20 μg/kg iv) immediately prior to LPS significantly inhibited all of these LPS-induced changes. To determine whether SOCS1 expression in cardiomyocytes is sufficient to inhibit LPS- and cytokine-induced expression of iNOS mRNA, the effects of forced expression of SOCS1 in cultured neonatal cardiomyocytes were investigated using an adenovirus-mediated transfection system. Forced expression of SOCS1 significantly inhibited iNOS transcription induced by LPS, tumor necrosis factor-α or interferon-γ. Conclusions CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression. (Circ J 2005; 69: 1412 - 1417)

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Background The mechanisms responsible for the development of pulmonary hypertension (PH) and pulmonary vascular structural remodeling induced by high pulmonary blood flow are not fully understood. The present study was designed to explore the possible changes in endogenous hydrogen sulfide (H₂S), a novel gasotransmitter, on the pathogenesis of PH and pulmonary vascular structural remodeling induced by high pulmonary blood flow. Methods and Results Twenty-two male Sprague-Dawley rats were randomly divided into a shunting group (n=11) and control group (n=11). Rats in the shunting group underwent an abdominal aorta-inferior cava vein shunting operation. After 11 weeks of shunting, the plasma level of H₂S and lung tissue H₂S producing rate were much lower than those of the control group (p<0.01). In situ hybridization analysis showed that the expression of cystathionine γ-lyase (CSE) mRNA was down-regulated in the pulmonary arteries of the shunting rats compared with the control group (p<0.01), and competitive quantitative reverse transcription-polymerase chain reaction showed that the relative amount of CSEmRNA in lung tissue was decreased significantly (p<0.01). Conclusions The endogenous H₂S pathway is down-regulated in PH and pulmonary vascular structural remodeling is induced by high pulmonary blood flow. (Circ J 2005; 69: 1418 - 1424)

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Pre-clinical Cushing's syndrome (pre-CS) is sometimes seen with adrenal cortical tumors. An 80-year-old woman had severe hypertension and hypokalemia, the typical clinical features of primary aldosteronism, but detailed hormonal examinations revealed the accompanying pre-CS. After adrenalectomy by laparoscopy, her blood pressure was remarkably reduced and the hypokalemia also recovered. The tumor consisted of mostly light clear cells and scattered dark compact cells resembling islands. Abundant expression of cytochrome P450 aldosterone synthase in the clear cells and cytochrome P450 11β-hydroxylase in the dark cells was detected by immunohistochemical studies, which confirmed that clear cells can produce aldosterone and compact cells can produce cortisol. (Circ J 2005; 69: 1425 - 1427)

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