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.

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.

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.