Factors associated with perceived feasibility and willingness of non-psychiatric doctors in Japan to treat depressed patients.

OBJECTIVES: We previously reported that many non-psychiatric doctors in Japan believe that treating depression was not part of their duties. Educational interventions must address motivation of physicians to play a role in depression care. In this study, we explored factors associated with perceived feasibility and willingness of non-psychiatric doctors in Japan to treat depression. METHODS: The study population included non-psychiatric doctors of the General Physician-Psychiatrist (G-P) Network group in Japan. We explored perceived feasibility and willingness to treat depressed patients, and examined preliminary associations with attitudes toward depression (the Depression Attitude Questionnaire: DAQ) and current depression treatment in routine medical practice. RESULTS: Responses were obtained from 56 non-psychiatric doctors (response rate: 35.4%). The doctors who scored high on the "Professional" and "Pessimism" subscale of the DAQ believed that treating depressed patients was not feasible (chi2 = 13.6, p < 0.01; chi2 = 7.3, p < 0.05, respectively) and were not willing to treat depressed patients (chi2 = 9.4, p < 0.01; chi2 = 6.6, p < 0.05, respectively) as part of their routine medical practice. The doctors who scored high on the "Professional" subscale referred fewer depressed patients to psychiatrists (r = -0.33, p < 0.05), and those who scored high on the "Pessimism" subscale recognized fewer depressed patients (r = -0.39, p < 0.01). CONCLUSIONS: The present study showed that attitudes toward depression were associated with perceived feasibility and willingness to treat depressed patients and with under-diagnosis of depression. Educational interventions optimized for these attitudes should be developed to improve recognition and treatment of depression in Japan.

Amlodipine has a preventive effect on temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker.

PURPOSE: We previously reported that α- and ß-blockers protected against emotional stress-induced cardiac dysfunction, but the protective effects of other antihypertensive drugs is unknown. The purpose of this study is to evaluate the ability of a calcium channel blocker, amlodipine, to prevent temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker, olmesartan medoxomil. METHODS: Rats premedicated with amlodipine (0.2 mg/kg), olmesartan (0.8 mg/kg), or vehicle were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress and then anesthetized to release stress. We measured the fractional area change (FAC) using echocardiography (SONOS5500) with a s12 probe (frequency 5-12 MHz, frame rate 120 Hz) and blood pressure and heart rate at the end of IMO and every 10 for 60 min after IMO. RESULTS: During IMO, FAC in the amlodipine or the olmesartan group was as high as that in the vehicle group. At 20 min after IMO, FAC in the amlodipine group was significantly higher than in the other two groups (84 ± 8 vs. 60 ± 7 or 68 ± 15 %, p < 0.05). During IMO, blood pressure in the amlodipine or the olmesartan group was significantly lower than with vehicle (119 ± 6 and 110 ± 7 vs. 124 ± 5 mmHg, p < 0.05). After IMO, blood pressure in the olmesartan group was significantly lower than in the other two groups. CONCLUSION: Acute administration of amlodipine could prevent a sudden drop in cardiac function after acute stress like IMO, but olmesartan did not. Amlodipine might have a protective effect on temporal left ventricular hypokinesia after emotional stress, which might not be related to decreased blood pressure.

Acute effects of beta-blocker with intrinsic sympathomimetic activity on stress-induced cardiac dysfunction in rats.

BACKGROUND: We have reported that α and ß adrenergic blockers could protect against emotional stress-induced cardiac dysfunction but those protective effects of ß adrenergic blockers with intrinsic sympathomimetic activity (ISA), such as celiprolol, are unknown. The purpose of this study is to evaluate whether ISA could relate with this protective effect. METHODS AND RESULTS: Rats medicated with celiprolol (8 mg/kg), metoprolol (4 mg/kg), or vehicle, were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress, and anesthetized to release stress. We measured the fractional area change (FAC) using an echocardiography (SONOS5500) with s12 probe (frequency: 5-12 MHz, frame rate: 120 Hz) at the end of IMO and every 10 min for 1h. During IMO, FAC in rats with a premedication of metoprolol was lower than in those with a premedication of vehicle or celiprolol. At 20 min after IMO, FAC in rats with a premedication of celiprolol was significantly higher than that with a premedication of metoprolol or vehicle (84 ± 9% vs. 65 ± 3% or 60 ± 7%, p<0.05). At 60 min after IMO, FAC in rats with a premedication of vehicle or celiprolol recovered, but FAC in rats with a premedication of metoprolol did not. CONCLUSION: Acute premedication with celiprolol could prevent a sudden drop of cardiac function after acute stress such as IMO. ISA might have an important role in preventing stress-induced cardiac dysfunction.

Attitudes toward depression among Japanese non-psychiatric medical doctors: a cross-sectional study.

BACKGROUND: Under-recognition of depression is common in many countries. Education of medical staff, focusing on their attitudes towards depression, may be necessary to change their behavior and enhance recognition of depression. Several studies have previously reported on attitudes toward depression among general physicians. However, little is known about attitudes of non-psychiatric doctors in Japan. In the present study, we surveyed non-psychiatric doctors' attitude toward depression. METHODS: The inclusion criteria of participants in the present study were as follows: 1) Japanese non-psychiatric doctors and 2) attendees in educational opportunities regarding depression care. We conveniently approached two populations: 1) a workshop to depression care for non-psychiatric doctors and 2) a general physician-psychiatrist (G-P) network group. We contacted 367 subjects. Attitudes toward depression were measured using the Depression Attitude Questionnaire (DAQ), a 20-item self-report questionnaire developed for general physicians. We report scores of each DAQ item and factors derived from exploratory factor analysis. RESULTS: We received responses from 230 subjects, and we used DAQ data from 187 non-psychiatric doctors who met the inclusion criteria. All non-psychiatric doctors (n = 187) disagreed with "I feel comfortable in dealing with depressed patients' needs," while 60 % (n = 112) agreed with "Working with depressed patients is heavy going." Factor analysis indicated these items comprised a factor termed "Depression should be treated by psychiatrists" - to which 54 % of doctors (n = 101) agreed. Meanwhile, 67 % of doctors (n = 126) thought that nurses could be useful in depressed patient support. The three factors derived from the Japanese DAQ differed from models previously derived from British GP samples. The attitude of Japanese non-psychiatric doctors concerning whether depression should be treated by psychiatrists was markedly different to that of British GPs. CONCLUSIONS: Japanese non-psychiatric doctors believe that depression care is beyond the scope of their duties. It is suggested that educational programs or guidelines for depression care developed in other countries such as the UK are not directly adaptable for Japanese non-psychiatric doctors. Developing a focused educational program that motivates non-psychiatric doctors to play a role in depression care is necessary to enhance recognition and treatment of depression in Japan.

Azelnidipine, unique calcium channel blocker could prevent stress-induced cardiac dysfunction like α·ß blocker.

BACKGROUND: We have reported that α and ß adrenergic blockers could protect against emotional stress-induced cardiac dysfunction. Azelnidipine is a unique calcium blocker which does not increase heart rate. The purpose of this study is to evaluate the effect of azelnidipine to prevent stress-induced cardiac dysfunction. METHODS AND RESULTS: Rats premedicated with azelnidipine (0.3 mg/kg), labetalol (3 mg/kg), or vehicle, were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress, and anesthetized to release stress. We measured the fractional area change (FAC) by echocardiography, blood pressure, and heart rate at the end of IMO and every 10 min for 60 min after IMO. During IMO, FAC in the labetalol group was significantly lower than that in the other two groups. At 20 min after IMO, FAC in the azelnidipine or labetalol group was significantly higher than that in the vehicle group (86 ± 9%, 73 ± 5% vs. 56 ± 11%, p<0.05). During IMO, mean blood pressure in the azelnidipine or labetalol group was significantly lower than that in the vehicle group (107 ± 5 mmHg, 106 ± 17 mmHg vs. 124 ± 5 mmHg, p<0.05). CONCLUSION: Acute administration of azelnidipine could prevent a sudden drop of cardiac function after acute stress like IMO. Azelnidipine might have a protective effect on stress-induced cardiac dysfunction like α and ß adrenergic blockers.

Monocrotaline-induced pulmonary hypertension with sufficient tricuspid regurgitation in a rat model.

BACKGROUND AND PURPOSE: It is well known that monocrotaline (MCT) induces pulmonary hypertension (PH) in rats. This model is very useful for understanding the physiology of PH and developing treatments for PH. However, it is very difficult to estimate pulmonary artery pressure (PAP) in this model. The purpose of this study is to establish a PH model with sufficient tricuspid regurgitation (TR) to evaluate PAP. METHOD: We studied 17 male rats that received 15 injections of 5 mg/kg/day of MCT (PH) or vehicle (control). Three weeks after the first MCT injection, we measured left and right ventricular dimensions, the ratio of acceleration to ejection time in pulmonary flow, and the development of TR using an echocardiograph (SONOS5500) with a s12 probe (frequency: 5-12 MHz, frame rate: 120 Hz). RESULTS: The right ventricular end-diastolic area in the PH group was significantly larger than that in the control group. The acceleration time/ejection time ratio and velocity time integral of the pulmonary artery in the PH group were smaller than those in the control group. In 78 % of rats in the PH group, sufficient TR was observed and estimated PAP was 75.4 ± 13.8 mmHg. There was a good correlation between PAP estimated by a Doppler method and directly measured right ventricular pressure (r = 0.94, P < 0.0001). CONCLUSION: Fifteen injections of 5 mg/kg/day of MCT could induce PH with sufficient TR in rats. Transthoracic echocardiography could be used for monitoring the progress of PH in the rat model.

Evaluation of left ventricular rotation by two-dimensional speckle tracking method and real-time three-dimensional echocardiography: comparison with MRI tagging method.

BACKGROUND: Recently, it has become possible to evaluate left ventricular (LV) torsion by two-dimensional (2D) speckle tracking images. However, LV torsion is a three-dimensional (3D) performance, which per se cannot be assessed by the 2D speckle tracking method. The present study investigated the accuracy of the 2D speckle tracking method and real-time 3D echocardiography in measuring LV rotation, comparing with the MRI tagging method. METHODS: We assessed LV apical rotation using the 2D speckle tracking method, real-time 3D echocardiography, and MRI tagging method in 26 normal subjects, and compared the results of these three methods. LV apical rotation was measured just before the level in which the posterior papillary muscle was absorbed into the free wall. RESULTS: The degree of LV apical rotation evaluated by the 2D speckle tracking method (Δθ 2D) was significantly smaller than that evaluated by 3D echocardiography (Δθ 3D) and the MRI tagging method (Δθ MRI) (Δθ 2D 7.3 ± 2.8°; Δθ 3D 8.8 ± 3.4°; Δθ MRI 9.0 ± 3.4°; Δθ 2D vs. Δθ 3D, p = 0.0001; Δθ 2D vs. Δθ MRI, p < 0.0001). There were good correlations among Δθ 2D, Δθ 3D, and Δθ MRI, but agreement between Δθ 3D and Δθ MRI (mean difference 0.14 ± 1.43°) was better than that between Δθ 2D and Δθ MRI (mean difference 1.68 ± 1.89°). CONCLUSION: The degree of LV apical rotation was underestimated with the 2D speckle tracking method compared with the MRI tagging method, whereas it could be precisely measured by 3D echocardiography.

Assessment of myocardial ischemic memory using persistence of post-systolic thickening after recovery from ischemia.

OBJECTIVES: We sought to investigate the time course of post-systolic thickening (PST) and systolic abnormality after recovery from brief myocardial ischemia. BACKGROUND: Myocardial ischemic memory imaging, denoting the visualization of abnormalities provoked by ischemia and sustained even after restoration of perfusion, is desirable and allows after-the-fact recognition of ischemic insult. PST offers a sensitive marker of myocardial ischemia, but whether this abnormal thickening remains after relief from brief ischemia is unclear. METHODS: Tissue strain echocardiographic data were acquired from 27 dogs under 2 different conditions of myocardial ischemia induced by either brief coronary occlusion (15 or 5 min) followed by reperfusion (Protocol 1) or by dobutamine stress during nonflow-limiting stenosis (Protocol 2). Peak systolic strain and post-systolic strain index (PSI), a parameter of PST, were analyzed. RESULTS: In Protocol 1, peak systolic strain was significantly decreased in the risk area during occlusion. This decrease in peak systolic strain in the 15-min group did not completely recover to baseline levels even 120 min after reperfusion, whereas the decrease in the 5-min group recovered immediately after reperfusion. We found that PSI was significantly increased during occlusion, but increased PSI in the 5-min group remained until 30 min after reperfusion (-0.19 +/- 0.18 [baseline] vs. 0.19 +/- 0.14 [30 min], p < 0.05) despite the rapid recovery of peak systolic strain. In Protocol 2, increased PSI was sustained until 20 min after the end of dobutamine infusion (-0.26 +/- 0.11 [baseline] vs. -0.16 +/- 0.10 [20 min], p < 0.05), although peak systolic strain recovered by 5 min after the end of dobutamine infusion. CONCLUSIONS: PST remained longer than abnormal peak systolic strain after recovery from ischemia. Assessment of PST may be valuable for detecting myocardial ischemic memory.

Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic.

Recently, middle-aged men who have begun frequently complaining of erectile dysfunction and nonspecific symptoms similar to those of postmenopausal women, visited a male climacterium clinic in Japan. Some patients, who were already taking antihypertensive medication, discontinued or reduced their dosages of antihypertensive medication after anti-depressant therapy. Forty-nine males over the age of 40 years were studied to evaluate the relationships between blood pressure, mental stress, and testosterone levels. The systemic blood pressure (sBP) of 24 patients was higher than the criteria for mild hypertension: 140/90 mmHg (HT group) at first visit. The sBP of the other 25 patients was normal (N group). The international index of erectile function (IIEF5) score (normal >21), self-rating depression scale (SDS) score (normal <40), and plasma testosterone levels were also evaluated before and after anti-depressant therapy without androgen replacement therapy. There were no significant differences between the groups in IIEF5 or SDS scores. The plasma testosterone levels in the HT group at first visit were significantly lower than those in the N group (230+/-77 vs. 343+/-92 ng/dL, p<0.001). After treatment, the IIEF5 scores were unchanged, whereas SDS scores were lower in both groups. Mean systemic blood pressure (mBP) in the HT group significantly decreased from 112+/-7 to 94+/-7 mmHg after treatment, concomitant with the disappearance of nonspecific complaints and the increase of testosterone levels. In the N group, however, neither mBP nor testosterone levels changed. Psychotherapy can ameliorate mild systemic hypertension in climacteric men with low testosterone levels. Mental stress might suppress the hypothalamic-pituitary-gonadal axis to decrease testosterone levels.

Effect of systemic blood pressure on microcollateral circulation evaluated by real-time contrast echocardiography.

BACKGROUND: In acute myocardial infarction, residual collateral-derived myocardial blood flow (CBF) within the ischemic area is one of the major determinants of infarct size. Management of systemic blood pressure (sBP) related to maintain collateral circulation is still difficult. The aim of this study was to reveal the influence of sBP on the rescue of area at risk by collateral circulation. METHODS: Real-time myocardial contrast echocardiography just after the onset of complete occlusion of the left circumflex coronary artery was performed in collateral-rich open-chest dogs. The video intensity of the ischemic area was evaluated during the occlusion and the CBF (A x beta) was calculated from a replenishment curve: y = A (1 - e(-beta t)). To analyze the effect of sBP on the collateral circulation, sBP was altered by infusion of nitroglycerin or etilefrine hydrochloride. To evaluate the defect size (%DS), every end-systolic myocardial contrast echocardiography image after left circumflex coronary artery occlusion was converted into binary images using custom offline software. RESULTS: The %DS increased and CBF slightly decreased at low sBP. The %DS decreased and CBF increased at high sBP. At excessively high sBP, %DS increased and CBF decreased again. CONCLUSION: Real-time myocardial contrast echocardiography, which is a useful noninvasive method to evaluate the collateral perfusion quantitatively, has a crucial role in the decision of patient treatment and management strategy of acute myocardial infarction.

Effect of sildenafil citrate (Viagra) on coronary flow in normal subjects.

BACKGROUND: The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. METHODS: The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). RESULTS: The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. CONCLUSION: Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects.

Assessment of dyssynchronous wall motion during acute myocardial ischemia using velocity vector imaging.

OBJECTIVES: The purpose of this study was to investigate the diagnostic value of velocity vector imaging (VVI) for detecting acute myocardial ischemia and whether VVI can accurately demonstrate the spatial extent of ischemic risk area. BACKGROUND: Using a tracking algorithm, VVI can display velocity vectors of regional wall motion overlaid onto the B-mode image and allows the quantitative assessment of myocardial mechanics. However, its efficacy for diagnosing myocardial ischemia has not been evaluated. METHODS: In 18 dogs with flow-limiting stenosis and/or total occlusion of the coronary artery, peak systolic radial velocity (V(SYS)), radial velocity at mitral valve opening (V(MVO)), peak systolic radial strain, and the percent change in wall thickening (%WT) were measured in the normal and risk areas and compared to those at baseline. Sensitivity and specificity for detecting the stenosis and occlusion were analyzed in each parameter. The area of inward velocity vectors at mitral valve opening (MVO) detected by VVI was compared to the risk area derived from real-time myocardial contrast echocardiography (MCE). Twelve image clips were randomly selected from the baseline, stenosis, and occlusions to determine the intra- and inter-observer agreement for the VVI parameters. RESULTS: The left circumflex coronary flow was reduced by 44.3 +/- 9.0% during stenosis and completely interrupted during occlusion. During coronary artery occlusion, inward motion at MVO was observed in the risk area. Percent WT, peak systolic radial strain, V(SYS), and V(MVO) changed significantly from values at baseline. During stenosis, %WT, peak systolic radial strain, and V(SYS) did not differ from those at baseline; however, V(MVO) was significantly increased (-0.12 +/- 0.60 cm/s vs. -0.96 +/- 0.55 cm/s, p = 0.015). Sensitivity and specificity of V(MVO) for detecting ischemia were superior to those of other parameters. The spatial extent of inward velocity vectors at MVO correlated well with that of the risk area derived from MCE (r = 0.74, p < 0.001 with a linear regression). CONCLUSIONS: The assessment of VVI at MVO permits easy detection of dyssynchronous wall motion during acute myocardial ischemia that cannot be diagnosed by conventional measurement of systolic wall thickness. The spatial extent of inward motion at MVO suggests the size of the risk area.

Quantitative assessment of microcollateral recruitment during coronary occlusion using real-time intravenous myocardial contrast echocardiography.

BACKGROUND: Residual collateral-derived myocardial blood flow (MBF) (A x beta) is important to protect against myocardial ischemia after acute coronary occlusion. METHODS: Recruitment of microcollateral was assessed in 22 dogs with left circumflex coronary artery occlusion by analysis of MBF and regional wall thickening (WT) using real-time myocardial contrast echocardiography. RESULTS: Video intensity and WT at the center of risk area were significantly lower than those at the border of risk area. The video intensity, A value, beta value, and MBF correlated well with WT after left circumflex coronary artery occlusion. The WT of the area with above 25% of normal MBF was preserved and was higher than that at below 25%. However, the deterioration of WT was not distinguished according to A value. CONCLUSION: Real-time myocardial contrast echocardiography is a useful noninvasive method to evaluate collateral-derived MBF, which can be a reliable index of protection against myocardial ischemia.

Three-dimensional reconstruction of coronary arteriole plexus image by contrast echocardiography using a high-frequency transducer.

OBJECTIVE: This study was established to examine the efficacy of a high-frequency liner probe for visualizing fine anatomy of coronary microcirculation. METHODS: The vessel size and its velocity-time integral at the anterior wall in dogs by real-time contrast echocardiography with high-frequency liner probe and pulse Doppler methods, and the coronary flow volume, were measured before and after adenosine triphosphate injection. A 3-dimensional (3D) image was reconstructed by the built-in 3D system using intermittent flash echocardiographic images. RESULTS: The increments of flow volume calculated from vessel sizes and velocity-time integral were well correlated with those of coronary flow volume. Using intermittent flash echocardiographic images, fine dots and lines of contrast echocardiographic-expected arterioles were evident, and easily and quickly reconstructed as coronary plexus by 3D system. CONCLUSION: A high-frequency liner probe provides the fine-vessel images to evaluate those morphologic changes; a 3D reconstruction image could provide new information about coronary arterioles.

Brief communications: visualization of coronary arteries in rats by 3-dimensional real-time contrast echocardiography.

Angiogenesis is under intense investigation to advance the treatment of various ischemic diseases. Small animals, such as mice and rats, are often used for this purpose. However, evaluating the structure of coronary arteries in small animals in situ is not easy. We succeeded in visualizing the coronary artery in rats on 3-dimensional real-time contrast echocardiography using a high-frequency transducer. These methods will be applied for more convenient assessment in a new study, examining issues such as angiogenesis using rats in situ.

Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack.

Emotional stress triggers takotsubo cardiomyopathy in postmenopausal women. Clinical analysis of autonomic nervous function has revealed a transient increase of sympathetic nervous activity and decrease of vagal nervous activity. Immobilization (IMO) stress of rats can reproduce the electrocardiographic and left ventriculographic changes that occur in takotsubo cardiomyopathy, both of which are prevented by combined blockade of alpha- and beta-adrenoceptors. Estrogen supplementation partially attenuated these cardiac changes. It also attenuated the IMO-induced increase of c-Fos immunoreactivity, or c-fos mRNA expression in the lateral septum, medial amygdaloid nucleus, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, laterodorsal tegmental nucleus, and locus ceruleus; these regions contain central sympathetic neurons and neurons with immunoreactive estrogen receptors. It also downregulated c-fos mRNA expression in the adrenal gland and the heart, suggesting an increase of estrogen attenuated the stress-induced hypothalamo-sympathoadrenal outflow from the central nervous system to the target organs. Estrogen treatment also upregulated the levels of cardioprotective substances, such as atrial natriuretic peptide and heat shock protein 70, in the heart. These data suggest that reduction of estrogen levels following menopause might be involved in the primary cause of takotsubo cardiomyopathy both by indirect action on the nervous system and by direct action on the heart.

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

BACKGROUND: Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. CONCLUSION: In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

[Myocardial perfusion abnormality induced by right ventricular pacing: real-time myocardial contrast echocardiography study].

BACKGROUND AND OBJECTIVES: False positive findings of coronary stenosis are frequently detected by exercise stress myocardial scintigraphy in patients with left bundle branch block (LBBB). We investigated the relationship between regional wall motion abnormality and myocardial perfusion abnormality at high right ventricular (RV) pacing rate in the region of the RV pacing (the ventricular septum) and the control region (the lateral wall) assuming exercise stress in patients with LBBB. METHODS: RV pacing was performed in 7 open chest canines. Real time myocardial contrast echocardiography of the left right ventricular short-axis view was examined by Toshiba Aplio during infusion of the ultrasound contrast agent (Definity). The examination was performed at baseline without pacing and at high RV pacing. Replenishment curve of the myocardial opacification was obtained and fit to the equation of y = A (1 - e (-betat)) in the regions of the ventricular septum and the lateral wall. Wall thickening ratio (%WT) was calculated in both regions. RESULTS: Dyssynchronous motion was observed during high RV pacing, but no wall motion abnormality was seen in control conditions. Although %WT, A-value and beta-value were almost identical between both regions at baseline, %WT and beta decreased in the ventricular septum at high RV pacing. The value did not differ between two regions. CONCLUSIONS: We concluded that perfusion abnormality occurs with regional wall motion abnormality at high RV pacing based on real time myocardial contrast echocardiography.

Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart.

BACKGROUND: Takotsubo cardiomyopathy is triggered by emotional or physical stress especially in post-menopausal women. A reduction in estrogen levels following menopause might underlie the high incidence of takotsubo cardiomyopathy. METHODS AND RESULTS: The left ventricular contraction between ovariectomized rats (OVX) and OVX with estrogen supplementation (OVX + E) while subjected to immobilization stress (IMO) was compared. The IMO in combination with general anesthesia impaired the left ventricular contraction in both OVX and OVX + E. Estrogen supplementation tended to improve the IMO-induced cardiac dysfunction and significantly attenuated the increase of blood pressure and heart rate. To understand the protective mechanism of estrogen, the expression of c-fos mRNA, a marker of cellular activation was compared. The mRNA expression of cardioprotective substances in the heart was also investigated. In the OVX + E, the levels of c-fos mRNA were significantly decreased in the paraventricular hypothalamic nucleus, adrenal gland and left ventricle, suggesting that an increase of estrogen attenuates the emotional stress-induced hypothalamo-sympatho-adrenal outflow from the central nervous system to the target organs. An expression of heat shock protein 70 and atrial natriuretic peptide was significantly augmented in the OVX + E. CONCLUSIONS: These data suggest that estrogen supplementation partially prevents emotional stress-induced cardiovascular responses both by indirect action on the nervous system and by direct action on the heart.