Fumio Yuasa

Factors associated with atrial fibrillation in Q wave anterior myocardial infarction

To elucidate the role of inflammatory and hemodynamic factors in the genesis of atrial fibrillation in acute myocardial infarction, 228 patients with a first Q wave anterior myocardial infarction were studied. Forty-nine patients had pericarditis (detection of pericardial rub by careful auscultation), and 36 patients had echocardiographically demonstrated hydropericardium (presence of pericardial effusion without pericardial rub). During the first 3 days after admission, transient episodes of atrial fibrillation were observed in 10 patients (20%) with pericarditis (group 1), 15 patients (42%) with hydropericardium (group 2), and 20 patients (14%) without pericarditis and hydropericardium (group 3). Although there was no significant difference in the incidence of atrial fibrillation between groups 1 and 3, patients in group 2 had a significantly higher incidence of atrial fibrillation than those in groups 1 and 3. Pulmonary capillary wedge pressure and the number of advanced asynergic segments were found to be the important factors discriminating the three groups by multivariate analysis. Therefore atrial fibrillation after acute Q wave anterior infarction was not related to the inflammatory infiltration involving the atria but to the increase in atrial pressure resulting from hemodynamic change caused by more extensive myocardial damage.

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.

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.

Cardiovascular adaptations to exercise training after uncomplicated acute myocardial infarction.

Motohiro M, Yuasa F, Hattori T, Sumimoto T, Takeuchi M, Kaida M, Jikuhara T, Hikosaka M, Sugiura T, Iwasaka T: Cardiovascular adaptations to exercise training after uncomplicated acute myocardial infarction. Am J Phys Med Rehabil 2005;84:684–691. 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.

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.

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.

Oxygen utilization, carbon dioxide elimination and ventilation during recovery from supine bicycle exercise 6 to 8 weeks after acute myocardial infarction

The pattern of oxygen (O2) consumption (VO2), carbon dioxide (CO2) production (VCO2), ventilatory and metabolic responses during and in recovery from supine bicycle exercise was examined in 18 patients with recent myocardial infarction. An increase in VO2 with increasing work load was accomplished by proportional increases in both cardiac output and the arteriovenous O2 difference. During recovery, however, the arteriovenous O2 difference rapidly decreased below levels at rest, whereas VO2 and cardiac output remained elevated, indicating that VO2 during recovery further depended on relatively high cardiac output. The ratio of VCO2 to VO2 further increased after exercise, suggesting that such cardiac output contributed to the remaining high CO2 flow to the lung and therefore enhanced ventilation. Increased arterial catecholamines during exercise remained elevated for the first 5 minutes of recovery. Arterial lactate during this period continued to increase and resulted in profound metabolic acidosis, causing alveolar hyperventilation after exercise. These results suggest that during recovery from exercise, cardiopulmonary responses remain enhanced because of continuing high cardiac output, resulting in subsequent high CO2 flow to the lung and metabolic acidosis, and that this may be associated with profound fatigue or dyspnea after exercise.

Importance of left ventricular diastolic function on maintenance of exercise capacity in patients with systolic dysfunction after anterior myocardial infarction

To investigate the role of left ventricular (LV) diastolic function in the maintenance of exercise capacity in patients with systolic dysfunction, symptom-limited cardiopulmonary exercise testing combined with radionuclide ventriculography was performed in 24 patients with an LV ejection fraction < 35% after anterior myocardial infarction. The ratio of pulmonary artery wedge pressure (PAWP) to LV end-diastolic volume (EDV), an index of global diastolic function, correlated significantly with peak oxygen consumption at peak exercise (r = -0.55; p = 0.006), whereas ejection fraction at peak exercise did not. The change in PAWP/EDV ratio from rest to peak exercise was related to the increases in stroke volume (r = -0.54; p = 0.006) and cardiac output (r = -0.51; p = 0.01) during exercise, but the change in ejection fraction was not. Resting hemodynamics did not differ between patients with preserved exercise capacity (group 1, n = 8) and those with exercise impairment (group 2, n = 16). At peak exercise, stroke volume, cardiac output, and EDV were significantly higher, and PAWP and PAWP/EDV ratio were significantly lower in group 1 than in group 2, but ejection fraction and end-systolic volume were similar in both groups. Although the incidences of hypertension, LV hypertrophy, and infarct-related coronary artery lesions did not differ between the two groups, group 2 had a significantly higher incidence of non-infarct-related coronary artery lesions than group 1 (p < 0.05). Thus in patients with LV systolic dysfunction after anterior myocardial infarction, the major cause of exercise impairment and failure to increase LV performance during exercise was diastolic dysfunction associated with the presence of non-infarct-related coronary artery lesions with the potential for exercise-induced ischemia of the noninfarcted areas.

Pericardial effusion after primary percutaneous transluminal coronary angioplasty in first Q-wave acute myocardial infarction

To evaluate the incidence and clinical significance of infarction-associated pericardial effusion in patients with successful primary percutaneous transluminal coronary angioplasty, we studied 214 consecutive patients with a first Q-wave acute myocardial infarction. Based on 9 clinical variables, multivariate analysis was performed to determine the important variables related to the occurrence of pericardial effusion. Pericardial effusion was detected by echocardiography in 45 patients (21%); pericardial rub (p <0.001), number of advanced asynergic segments (p <0.001), ventricular aneurysmal motion (p = 0.03), and pulmonary capillary wedge pressure (p = 0.04) were found to be the important variables related to pericardial effusion. Among 45 patients with pericardial effusion, 29 patients with no pericardial rub had significantly higher pulmonary capillary wedge pressure than those with pericardial rub, whereas 16 patients with pericardial rub had a higher incidence of angiographic no reflow and ventricular aneurysmal motion than those without pericardial rub. Patients with pericardial effusion and a pericardial rub had a higher mortality rate than those without pericardial effusion (19% vs 3%; p = 0.02). Thus, pericardial effusion is still a relatively common clinical finding after primary percutaneous transluminal coronary angioplasty, and those with pericardial effusion and a pericardial rub were associated with more severe transmural myocardial damage and higher in-hospital mortality.

Effects of left ventricular diastolic dysfunction on exercise capacity three to six weeks after acute myocardial infarction in men

To examine the effects of left ventricular (LV) diastolic dysfunction on exercise capacity, hemodynamic and radionuclide responses were measured at rest and during exercise in 50 patients with recent myocardial infarction. The ratio of an increase in pulmonary arterial wedge pressure (PAWP) to an increase in LV end-diastolic volume (EDV) from rest to peak exercise (delta PAWP/delta EDV) was used as an index of LV diastolic function, delta PAWP/delta EDV had modest and negative correlations with peak oxygen consumption (VO2), cardiac output, and stroke volume in all patients. Among patients with peak VO2 > or = 20 ml/min/kg (group I, n = 24) and those with peak VO2 < 20 ml/min/kg (group II, n = 26), there were no differences between the 2 groups with regard to resting LV ejection fraction, EDV, PAWP, cardiac output, and stroke volume. Although there was no significant difference in LV ejection fraction at peak exercise, group II had significantly reduced EDV, increased PAWP, and decreased cardiac output and stroke volume than those in group I. As a result, delta PAWP/delta EDV was significantly higher in group II. These results suggest that LV diastolic dysfunction has a key role in determining exercise capacity in patients with reduced exercise capacity after recent myocardial infarction.