Hiroshi Yokoe

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

Abstract: 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 &mgr;g/dL to 12.2 ± 7.1 &mgr;g/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.

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.

Previous Statin Therapy Improves Clinical Outcome of Patients withST-Segment Elevation Myocardial Infarction Undergoing PrimaryPercutaneous Coronary Intervention

Background: Statin treatment has been shown to reduce the risk of coronary artery disease and improve the outcome of patients with acute myocardial infarction. However, the effects of previous statin treatment on the clinical course of subsequent acute myocardial infarction remain unclear. This study was designed to investigate whether previous statin therapy influences the clinical outcome of patients with ST-Segment Elevation Myocardial Infarction (STEMI) treated with primary Percutaneous Coronary Intervention (PCI). Methods: We evaluated the clinical outcome of 350 patients with STEMI undergoing primary PCI, of which 91 received previous statin treatment (statin group) and 259 did not (non-statin group). Myocardial perfusion, infarct size, inflammatory responses, and Major Adverse Cardiovascular Events (MACE) were evaluated. Results: The frequency of MACE at 1 month after PCI was significantly lower in the statin group than the nonstatin group (4.4% vs. 13.9%, p=0.014). Post-PCI peak creatine kinase was significantly lower in the statin group median, (interquartile range): (1246 [504-3301] vs. 2235 [952-4083] IU/ml; p=0.002), whereas peak high-sensitivity C-reactive protein did not significantly differ between the two groups (p=0.287). The frequency of ST-segment resolution after PCI was significantly higher in the statin group (90.1% vs. 76.8%; p=0.006), as was the frequency of Thrombolysis in Myocardial Infarction grade 3 coronary flow (p=0.008). Myocardial blush grade was similar in both groups (p=0.839). Multivariate logistic regression analysis revealed previous statin treatment, hs-CRP, blood glucose, and age to be independent predictors of MACE. Conclusion: Previous statin therapy enhances coronary flow, reduces infarct size, and improves clinical outcome of STEMI patients treated with primary PCI.

Free-Floating Right Ventricular Thrombus as Assessed by Real-time 3-Dimensional Transesophageal Echocardiography

A 71-year-old woman being treated with predonine at a dose of 10 mg/d for rheumatoid arthritis had a short episode of syncope lasting a couple of minutes. Her physical examination on admission revealed clear consciousness, resting tachycardia of 96 beats per minute, blood pressure of 114/68 mm Hg, jugular venous distention, and edema of the dorsum of the right foot. Electrocardiography revealed sinus tachycardia and right axis deviation. Chest radiography showed no pulmonary congestion. Transthoracic echocardiography showed a moderately dilated right ventricle with impaired right ventricular systolic function containing a large freefloating echogenic mass. There was moderate tricuspid regurgitation with an estimated pulmonary artery pressure of 59/24 mm Hg. Subsequent investigation by real-time 3-dimensional transesophageal echocardiography revealed that the large floating right intraventricular mass was highly mobile (Figure 1A and Video 1) and attached to the chordal structures of the tricuspid valve, which was prolapsing through the pulmonary valve into the main pulmonary artery. The clinical suspicion of pulmonary thromboembolism was subsequently confirmed by lung perfusion scanning. Anticoagulation therapy with intravenous heparin was initiated, and urgent cardiac surgery was performed with complete removal of the thrombus (Figure 1B). Histopathologic examination of the removed material showed findings consistent with a thrombus. Long-term oral anticoagula-

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

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.

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.