Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 µg/dL to 12.2 ± 7.1 µg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

Radiofrequency catheter ablation of posterior paraseptal accessory pathway with atresia of the coronary sinus ostium.

A 42-year-old man was referred to our hospital for an electrophysiologic study because of recurrent episodes of palpitation. On coronary angiogram, an anomalous atresia of the coronary sinus (CS) ostium was discovered. The ablation catheter was inserted from the right femoral artery to the accessory pathway (AP) of posterior paraseptal area. The earliest retrograde atrial activation was recorded in the 5-6 o'clock region of the mitral annulus. Radiofrequency energy was delivered to this site, resulting in elimination of the AP. After this application, there was persistent ventriculoatrial dissociation and led to successful ablation of the AP.

Pseudoaneurysm with left-to-right shunt in a patient with myocardial infarction: evaluation by three-dimensional echocardiography.

It is often difficult to noninvasively differentiate a post-infarction left ventricular (LV) pseudoaneurysm from a post-infarction true aneurysm. A 66-year-old woman with a past history of inferior acute myocardial infarction was admitted to our hospital because of acute decompensated heart failure. Two-dimensional transthoracic echocardiography showed an aneurysm with a narrow orifice in the inferoposterior basal area. The pulmonary to systemic flow ratio (Q p/Q s) was 2.2:1, which corresponded to moderate left-right shunting. Three-dimensional transesophageal echocardiography (3D-TEE) showed the orifice in the perforated right ventricular basal area with a color jet through the orifice from the LV to the right ventricle. Collectively, based on the 3D-TEE findings, we diagnosed the case as inferoposterior pseudoaneurysm with a left-to-right shunt caused by myocardial infarction.

Left ventricular apical ballooning syndrome in a patient with infundibular stenosis of the right ventricle: A case report.

A 73-year-old female patient with a past history of right ventricular infundibular stenosis was admitted to our intensive care unit because of right ventricular dysfunction. On the fifth day of hospitalization, she suddenly experienced dyspnea without chest pain despite the improvement of her condition by initial medical treatment. Although electrocardiography revealed no ST-segment elevation, echocardiography and myocardial perfusion using 99mTc-MIBI revealed new development of severe symmetrical akinesia and reduced perfusion of the left ventricular (LV) apex and mid-ventricle. LV apical ballooning syndrome was diagnosed based on the minimal elevation of cardiac enzymes (peak cardiac troponin I 0.18 ng/ml) despite the presence of large regions of focal myocardial damage in the myocardium and the absence of positive ECG diagnosis and urgent coronary angiography. Previous coronary angiography revealed normal coronary arteries and the left anterior descending artery without full irrigation around the apex making apical ballooning. On the 12th day of hospitalization, despite the use of positive inotropic treatment, it was impossible to maintain hemodynamic stability, and the patient died prior to the functional recovery of the left ventricle.

Atypical morphology and myocardial perfusion of mid-ventricular ballooning: A case report.

Although some atypical types of transient left ventricular apical ballooning syndrome have been reported, only a few atypical types of transient mid-ventricular ballooning have been reported. A 70-year-old female underwent surgery for urothelial carcinoma. At day 5 after the surgery, she was admitted to our department without cardiac symptoms because of ST elevation in leads I, II, III, aVF and V1-V6 indicating acute coronary syndrome. She was diagnosed with stress induced cardiomyopathy based on an angiographically normal coronary artery, newly developed extensive wall motion abnormality (hyperbasal contraction and akinesis from the mid-left ventricle to the apex without hypercontraction of the small area adjacent to the apex) based on left ventriculography, and a small elevation of myocardial enzymes incongruous with the area of contraction abnormality. Myocardial scintigraphy with 99mTc-tetrofosmin showed a severely reduced myocardial perfusion in an extensive mid-ventricular area without a left ventricular base and top of apex, in accord with a wall motion abnormality different from typical apical ballooning or typical mid-ventricular ballooning previously diagnosed in our hospital. This is the first report presenting an atypical mid-ventricular ballooning based on the myocardial atypical perfusion findings.

Differences in the mode of presentation for acute coronary syndrome by pre-hospitalization medication, in relation to coronary risk factors, East-Osaka acute coronary syndrome (EACS) registry.

BACKGROUND: Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. METHODS AND RESULTS: We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. CONCLUSION: Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Left atrial volume by real-time three-dimensional echocardiography: validation by 64-slice multidetector computed tomography.

BACKGROUND: Left atrial (LA) enlargement has been acknowledged as a significant predictor of cardiovascular morbidity and mortality. METHODS: To evaluate the accuracy of two-dimensional and three-dimensional echocardiography for determining LA volume, LA volume measurements by echocardiography were compared with those measured by 64-slice multidetector computed tomography (MDCT) as a reference standard. RESULTS: Fifty-seven consecutive patients (mean age, 66 ± 11 years; 59% men) referred to echocardiography and MDCT on the same day were prospectively evaluated. LA volume by three-dimensional echocardiography was correlated closely with that by MDCT (r = 0.95, P < .0001), with 8% underestimation. LA volume by two-dimensional echocardiography was correlated less well with that measured by MDCT (r = 0.86, P < .0001) and consistently underestimated LA volume by 19%, particularly as the left atrium enlarged. CONCLUSIONS: LA volume assessment by three-dimensional echocardiography was correlated closely with that measured by MDCT, albeit with an 8% underestimation. Three-dimensional echocardiography is a feasible noninvasive method to evaluate LA volume.

A new protocol using sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography.

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality rates. Although a previous study reported that pretreatment with sodium bicarbonate is more effective than sodium chloride for prophylaxis of CIN, this has not been a universal finding. We performed a prospective randomized trial to investigate whether CIN can be avoided using sodium bicarbonate. In total 155 patients with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) who were undergoing coronary angiography were enrolled. We assigned patients to sodium chloride plus sodium bicarbonate (bicarbonate group, n = 78) or sodium chloride alone (chloride group, n = 77). Infusion of sodium bicarbonate at 1 ml/kg/hour continued from 3 hours before to 6 hours after coronary angiography. CIN was defined as a 25% increase in serum creatinine from baseline value or an absolute increase of ≥0.5 mg/dl, which appeared within 2 days of contrast. Baseline GFR was not significantly different between the 2 groups. Patients in the bicarbonate group had a higher GFR than those in the chloride group on day 2 (45.8 ± 13.4 vs 40.9 ± 14.6 ml/min/1.73 m(2), p = 0.031) and at 1 month (49.5 ± 14.7 vs 43.7 ± 15.5 ml/min/1.73 m(2), p = 0.019). CIN occurred in 10 patients (13%) in the chloride group but in only 2 patients (2.6%) in the bicarbonate group (p = 0.012). Sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of CIN and can lead to retention of better long-term renal function.

The effects of clonidine on arterial baroreflex sensitivity and cardiopulmonary baroreflex control of sympathetic nerve activity in patients with left ventricular dysfunction.

BACKGROUND: Clonidine is a potent sympatholytic drug with central neural effects. The aim of this study was to evaluate the effects of clonidine on arterial baroreflex sensitivity (BRS) and cardiopulmonary (CP) baroreflex control of muscle sympathetic nerve activity (MSNA) in patients with left ventricular (LV) dysfunction. METHOD: Twenty patients were randomly assigned to either clonidine or placebo groups (10 in each group). BRS (by phenylephrine method) and CP baroreflex (by lower body negative pressure) effects on sympathetic nerve activity (circulating norepinephrine and MSNA recordings) were measured before and after a 4-week treatment period. RESULTS: Clonidine lowered blood pressure and heart rate. Clonidine was accompanied not only by a decrease in plasma noradrenaline (from 444±196 to 260±144 pg ml(-1) ) but also by a reduction in directly measured MSNA (from 47±16 to 36±16 bursts min(-1) ). BRS increased significantly from 3·01±1·19 to 6·86±2·84 ms mmHg(-1) after clonidine. When expressed as per cent change in MSNA during CP baroreceptor stimulation, CP baroreflex control of MSNA was significantly increased from 9·26±8·93% to 28·83±11·96% after clonidine. However, there were no significant changes in the measured variables in the control group. CONCLUSION: Clonidine enhanced BRS and CP baroreflex control of MSNA while reducing baseline sympathetic activity in patients with LV dysfunction.

Relationship between arterial baroreflex sensitivity and exercise capacity in patients with acute myocardial infarction.

SUMMARY: To investigate the relationship between arterial baroreflex sensitivity (BRS) and exercise capacity, we examined arterial BRS and its relation to exercise capacity during upright bicycle exercise in 40 uncomplicated patients with acute myocardial infarction. Arterial BRS was measured 3 weeks (20 +/- 5 days) after acute myocardial infarction and assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the R-R interval. All patients underwent graded symptom-limited bicycle exercise with direct measurements of hemodynamic and metabolic measurements. In all patients, the average arterial BRS was 5.6 +/- 2.6 ms mmHg(-1). There were no significant correlations between arterial BRS and hemodynamic measurements at rest. However, arterial BRS was negatively related to systemic vascular resistance at peak exercise (r = -0.60, P = 0.0001) and percent change increase in systemic vascular resistance from rest to peak exercise (r = -0.45, P = 0.003), whereas arterial BRS was positively related to cardiac output (r = -0.48, P = 0.002) and stroke volume at peak exercise (r = 0.42, P = 0.007), and percent change increase in cardiac output (r = -0.55, P = 0.0002) and stroke volume from rest to peak exercise (r = 0.41, P = 0.008). Furthermore, arterial BRS had modest but significant correlations with peak oxygen consumption (r = -0.48, P = 0.002) and exercise duration (r = 0.35, P = 0.029), indicating that patients with better arterial BRS have better exercise capacity in patients with acute myocardial infarction. These results suggest that arterial BRS was linked to central and peripheral hemodynamic responses to exercise and hence, contributed to exercise capacity after acute myocardial infraction.

Factors associated with myocardial salvage immediately after emergent percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

OBJECTIVE: The amount of myocardial salvage after percutaneous coronary intervention (PCI) is reported to be a major determinant of functional recovery in patients with ST-elevation acute myocardial infarction (MI). However, factors related to the amount of myocardial salvage remain unknown. The goal of this study was to investigate the factors related to the amount of myocardial salvage after emergent PCI in patients with ST-elevation acute MI by incorporating pre- and post-treatment indices and adjunctive treatments. METHODS: Technetium-99m myocardial imaging was performed before, immediately after, and one month after emergent PCI in 161 patients with ST-elevation acute MI, and the defect score was serially evaluated. A good myocardial salvage was defined as >/=4 change (before minus immediately after PCI) of the defect score. RESULTS: Good myocardial salvage was observed in 89 patients. Based on nine clinical variables, logistic regression analysis was performed to determine the important variables related to myocardial salvage. Multivariate analysis revealed that earlier time from onset to PCI (chi (2) = 6.55, P = 0.01, odds ratio = 2.78), larger defect score before PCI (chi (2) = 7.29, P = 0.01, odds ratio = 1.13) and administration of nicorandil before PCI (chi (2) = 9.88, P = 0.008, odds ratio = 4.42) were independently associated with good myocardial salvage. Thrombolysis In Myocardial Infarction (TIMI) flow grade <2 before PCI (chi (2) = 4.91, P = 0.03, odds ratio = 0.36) and TIMI flow grade

Augmented sympathoinhibitory effect of valsartan when added to angiotensin-converting enzyme inhibitor in patients with left ventricular dysfunction.

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the sympathetic nerve activity in patients with left ventricular (LV) dysfunction. The aim of this study was to examine the effect of ARBs on sympathetic nerve activity and baroreflex function in patients with LV dysfunction already receiving ACE inhibitors. METHODS: Twenty patients with LV dysfunction already treated with ACE inhibitor (enalapril 5 mg/day) were randomly divided into two groups: treatment with 10 mg/day enalapril (control group) or 5 mg/day enalapril plus 80 mg/day valsartan (combination group). In both groups, resting muscle sympathetic nerve activity (MSNA; microneurography), arterial baroreflex sensitivity, and cardiopulmonary baroreflex sensitivity were measured at baseline and 4 weeks after the treatment. Arterial baroreflexes were perturbed by phenylephrine method, and cardiopulmonary baroreflexes were perturbed by lower body negative pressure (-10 mmHg). RESULTS: Baseline characteristics in both groups were similar. Resting MSNA decreased significantly from 35.4+/-10.8 to 26.4+/-5.1 burst/min (p<0.05), while arterial baroreflex sensitivity improved significantly from 6.0+/-2.0 to 10.1+/-2.6 ms/mmHg in the combination group. Moreover, cardiopulmonary baroreflex control of MSNA improved significantly from 15.8+/-12.2 to 42.0+/-26.7% (p<0.05) in the combination group. However, there were no significant changes in arterial baroreflex sensitivity and cardiopulmonary baroreflex of MSNA in the control group. CONCLUSION: Addition of ARB to ACE inhibitor treatment reduced sympathetic nerve activity and augmented arterial and cardiopulmonary baroreflex sensitivity in patients with LV dysfunction.

Resting muscle sympathetic nerve activity, cardiac metaiodobenzylguanidine uptake, and exercise tolerance in patients with left ventricular dysfunction.

BACKGROUND: Sympathetic nerve overactivity and reduced exercise tolerance are characteristic features of patients with heart failure. However, to what extent sympathetic nerve overactivity contributes to limiting exercise tolerance has not been clearly defined. METHODS: Myocardial iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and cardiopulmonary exercise testing were performed within 3 days in 30 patients with left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was recorded by microneurography. RESULTS: The patients with peak VO(2) < 20 mL/minute/kg (group II, n = 15) had significantly higher MSNA and WR, and lower H/M ratio than those with peak VO(2) > or = 20 mL/minute/kg (group I, n = 15) (P < .05). Peak VO(2) had negative correlations with MSNA and WR (r = 0.58, 0.56), and positive correlations with early H/M ratio and delayed H/M ratio (r = 0.71, 0.75) in group II. Moreover, MSNA had negative correlations with early H/M ratio and delayed H/M ratio (r = 0.78, 0.66), and a positive correlation with WR (r = 0.79) in group II. However, similar relations were not found in group I. CONCLUSIONS: A link between cardiac and peripheral sympathetic nerve activities contributed to limiting exercise tolerance in patients with LVD patients and reduced exercise tolerance.

Cardiovascular adaptations to exercise training after uncomplicated acute myocardial infarction.

OBJECTIVE: This study examined the cardiovascular adaptations of an exercise training program and evaluated the role of peripheral vasodilator capacity in contributing to these adaptations after myocardial infarction. DESIGN: A total of 44 consecutive patients with uncomplicated myocardial infarction underwent 3 wks of exercise training. Controls (n = 12) with comparable myocardial infarction were selected from our database and were restricted to a program with minimal activity. All patients performed cardiopulmonary exercise testing with hemodynamic measurements. Forearm and calf reactive hyperemic flow were measured by venous occlusive plethysmography as indices of peripheral vasodilator capacity. RESULTS: Despite no change in arteriovenous oxygen difference at peak exercise after training, training resulted in significant increases in oxygen consumption, cardiac output, and stroke volume and a significant decrease in systemic vascular resistance at peak exercise (overall, P < 0.05). Calf reactive hyperemic flow increased significantly after training (P < 0.001), but forearm reactive hyperemic flow did not. Furthermore, increase in calf reactive hyperemic flow after training had a positive correlation with increases in peak cardiac output, stroke volume, and oxygen consumption after training and an inverse correlation with peak systemic vascular resistance. CONCLUSIONS: Exercise training improved exercise tolerance by improving hemodynamic responses to exercise after myocardial infarction. This improved exercise performance was linked to a training-induced increase in calf vasodilator capacity.

Hepatocyte growth factor delivered by ultrasound-mediated destruction of microbubbles induces proliferation of cardiomyocytes and amelioration of left ventricular contractile function in Doxorubicin-induced cardiomyopathy.

At present, there is no curative strategy for advanced cardiomyopathy except for cardiac transplantation, which is not easily performed, mainly due to a shortage of donors. It has been reported that myocardial progenitor cells exist even in the postnatal heart, suggesting that myocardial progenitor cells could proliferate under some situations and might improve cardiac function in cardiomyopathy-induced hearts. In this study, recombinant human hepatocyte growth factor (rhHGF) was delivered using ultrasound-mediated destruction of microbubbles (UMDM) into the cardiomyopathy-induced heart by doxorubicin (20 mg/kg). Intravenous injection of rhHGF (IV-rhHGF) alone or UMDM alone failed to improve the morphology or the function of the cardiomyopathy-induced heart, but (IV-rhHGF + UMDM) treatment significantly improved the heart morphologically and functionally, and repetitive treatments of (IV-rhHGF + UMDM) enhanced the effects. The number of bromodeoxy-uridine-positive cardiomyocytes significantly increased in the (IV-rhHGF + UMDM)-treated hearts compared with the untreated hearts. Moreover, Sca-1+ myocardial progenitor cells express c-Met, a receptor for HGF. These results suggest that (IV-rhHGF + UMDM) treatment could morphologically and functionally improve the heart in the case of doxorubicin-induced cardiomyopathy through the proliferation of the myocardial progenitor cells.

Correlation of heart rate turbulence with sympathovagal balance in patients with acute myocardial infarction.

To examine the relationship among heart rate turbulence parameters, arterial baroreflex sensitivity, and cardiac sympathetic nerve activity, 15 patients with acute myocardial infarction, presenting with sinus rhythm and > or = 3 ventricular premature beats/24 hr were studied at least 2 weeks after acute myocardial infarction. Turbulence onset (TO) and turbulence slope (TS) were averaged from 3 respective ventricular premature beats. Early heart-to-mediastinum ratio (H/M), delayed H/M, and washout rate were calculated from iodine-123-metaiodobenzylguanidine (123I MIBG) scintigraphy. Arterial baroreflex sensitivity was calculated by phenyrephrine method. Arterial baroreflex sensitivity correlated significantly with TO (r = - 0.75, p < .01) and TS (r = 0.53, p < .05). TO had no correlations with early H/M, delayed H/M, and washout rate. There were no significant correlations between TS and early H/M. However, TS had significant correlation with delayed H/M (r = 0.74, p < .01) and washout rate (r = -0.71, p < .01). Thus, heart rate turbulence of TO and TS parameters depend on sympathovagal balance.

The effect of residential exercise training on baroreflex control of heart rate and sympathetic nerve activity in patients with acute myocardial infarction.

STUDY OBJECTIVES: Exercise training has been shown to favorably affect the prognosis after acute myocardial infarction (AMI), but the mechanisms of such favorable effects remain speculative. The aim of this study was to determine whether exercise training improves baroreflex control of heart rate and muscle sympathetic nerve activity (MSNA) in patients with AMI. DESIGN: Prospective randomized clinical study. PARTICIPANTS: Thirty patients with an uncomplicated AMI were randomized into trained or untrained groups. Arterial BP, heart rate, and MSNA were measured at rest, and during baroreceptor stimulation (phenylephrine infusion) and baroreceptor deactivation (nitroprusside infusion). These measurements were performed at baseline and after 4 weeks of exercise training. MEASUREMENTS AND RESULTS: Peak oxygen uptake increased significantly (12.3 +/- 10.7% [mean +/- SD]) with exercise training. Resting MSNA reduced from 34 +/- 12 to 27 +/- 8 bursts/min in the trained group but not in the untrained group. Arterial baroreflex sensitivity (BRS) [from 8.9 +/- 3.0 to 10.3 +/- 3.0 ms/mm Hg, p < 0.05] and MSNA response to baroreceptor stimulation (change of integrated MSNA from - 47 +/- 23 to - 70 +/- 21%, p < 0.01) improved significantly in the trained group, but not in the untrained group. Despite baroreceptor deactivation improving MSNA response in both groups, there was no significant difference between the two groups. CONCLUSIONS: Exercise training increased arterial BRS and decreased sympathetic nerve traffic after AMI, which indicate that the sympathoinhibitory effect of exercise training may, at least in part, contribute to the beneficial effect of exercise training in patients with AMI.

Iodine 123-metaiodobenzylguanidine imaging reflect generalized sympathetic activation in patients with left ventricular dysfunction.

BACKGROUND: Iodine 123-metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. To determine the role of MIBG imaging as a measure of generalized sympathetic nerve activity, MIBG imaging was evaluated with muscle sympathetic nerve activity (MSNA) and plasma norepinephrine (noradrenaline) level in patients with old myocardial infarction. METHODS: Myocardial MIBG scintigraphy, MSNA and plasma norepinephrine measurement were performed within 3 days in 35 patients with old myocardial infarction. Patients were divided into three groups according to their ejection fraction (EF); preserved (EF > or = 50%, 12 patients), intermediate (35% < EF < 50%, 13 patients), or depressed (EF < or = 35%, 10 patients). The heart to mediastinum (H/M) ratio was obtained 4 h after tracer injection from the chest anterior view image. MIBG washout rate was calculated from the early and delayed images. MSNA was recorded by microneurography. RESULTS: Plasma norepinephrine level had weak negative correlations with early H/M ratio (r = 0.37, P<0.05) and delayed H/M ratio (r = 0.33, P<0.05), and a positive correlation with MIBG washout rate (r = 0.54, P<0.01). MSNA had weak negative correlations with early H/M ratio (r = 0.51, P<0.05) and delayed H/M ratio (r = 0.52, P<0.05). However, a strong correlation was found between MSNA and MIBG washout rate (r = 0.88, P<0.001). Despite no significant differences in plasma norepinephrine level and H/M ratio, patients with intermediate and depressed EF had higher MIBG washout rate and MSNA compared with those with preserved EF. CONCLUSIONS: Increased in cardiac sympathetic nerve activity was associated with augmented sympathetic outflow of the skeletal muscle and hence, MIBG washout rate allow the assessment of general sympathetic nerve activity.

Candesartan and arterial baroreflex sensitivity and sympathetic nerve activity in patients with mild heart failure.

The purpose of this study was to investigate the effects of candesartan on arterial baroreflex sensitivity (BRS) and sympathetic activity in patients with mild heart failure (HF). Arterial pressure, heart rate, plasma renin activity, plasma angiotensin II and noradrenaline, and muscle sympathetic nerve activity (MSNA) were measured before therapy and after 4 weeks in 20 patients with mild HF. Patients were assigned to a candesartan group (n = 10) or a placebo group (n = 10). Baroreflex sensitivity was assessed by using phenylephrine. Candesartan induced an increase in plasma renin activity and plasma angiotensin II associated with a reduction in arterial pressure without affecting heart rate. Although plasma noradrenaline was unchanged (320 +/- 322 pg/ml to 339 +/- 104 pg/ml), MSNA decreased significantly (52 +/- 11 bursts/min to 42 +/- 9 bursts/min; p < 0.01)) and BRS increased significantly (6.9 +/- 3.6 msec/mm Hg to 10.2 +/- 3.3 msec/mm Hg; p < 0.01) after candesartan. However, there were no significant changes in the measured variables in the placebo group. These data indicate that candesartan treatment enhanced BRS and reduced sympathetic activity in patients with mild HF. Thus, the inhibitory effect of candesartan on sympathetic activity may, at least in part, contribute to the beneficial effect of angiotensin II receptor blockade in patients with mild HF.