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Biomedical subjects

Yoichi Goto

Publications and source records attributed to Yoichi Goto.

At least 37 records · Page 2Linked to original sources

Successful treatment of refractory vasospastic angina with corticosteroids: coronary arterial hyperactivity caused by local inflammation?

BACKGROUND: Although vasospastic angina usually responds well to treatment with calcium antagonists and/or nitrates, there have been anecdotal case reports of refractory vasospastic angina resistant to intensive treatment with high doses of calcium antagonists and nitrates. METHODS AND RESULTS: Four patients with vasospastic angina, which was refractory to intensive treatment with high doses of calcium antagonists and nitrates, were completely controlled after administration of corticosteroids. Although none of the 4 patients showed eosinophilia, all had bronchial asthma or chronic thyroiditis, and in 2 cases, the activity of vasospastic angina corresponded with that of bronchial asthma. CONCLUSIONS: These findings suggest that in these patients, coronary spasm may have been induced by arterial hyperreactivity because of local inflammation in the coronary arterial wall and that the corticosteroids suppressed the arterial hyperreactivity by alleviating the inflammation. Corticosteroids may be considered as a treatment choice for patients with refractory vasospastic angina, particularly when the patient has an allergic tendency, such as bronchial asthma.

Adrenal Cortex Hormones↗

Exercise-induced hepatocyte growth factor production in patients after acute myocardial infarction: its relationship to exercise capacity and brain natriuretic peptide levels.

BACKGROUND: The hepatocyte growth factor (HGF) is a multifunctional cytokine with cardioprotective properties and potent myogenic activity for vascular endothelium. In patients after acute myocardial infarction, exercise training has the beneficial effects on cardiovascular adaptations. We hypothesized that exercise induces HGF production in those patients. If this hypothesis is correct, HGF production may be associated with clinical parameters of cardiovascular function. METHODS AND RESULTS: In 20 patients after acute myocardial infarction, HGF levels in the pulmonary artery (HGF(PA)) and aorta (HGF(Ao)) were determined at rest and during supine submaximal exercise, with cardiac output (CO) measured by catheterization. Exercise-induced HGF production was calculated by using the following equation: [(HGF(PA)-HGF(Ao))xCO during exercise]-[(HGF(PA)-HGF(Ao))xCO at rest]. On a separate day, peak oxygen uptake (VO2) was determined during a symptom-limited upright cardiopulmonary exercise test. Exercise increased HGF production (from 1.6 +/- 3.0 to 9.0 +/- 6.3 microg/ml, p<0.001). Exercise-induced HGF production was inversely related to peak VO2 (r=-0.664, p<0.01) and positively related to levels of brain natriuretic peptide (BNP), a biochemical marker for post-infarction ventricular remodeling (r=0.686, p<0.01). CONCLUSIONS: Exercise significantly increases HGF production. This phenomenon may play an important role in post-infarction patients, particularly with reduced exercise tolerance and elevated BNP levels.

Aged↗

Local delivery of argatroban for the prevention of restenosis after coronary balloon angioplasty: a prospective randomized pilot study.

BACKGROUND: Effective pharmacological prevention of restenosis using the systemic administration of various drugs that were effective for the prevention of restenosis in experimental studies has not been reported. The purpose of this study was to evaluate whether the local delivery of a potent thrombin inhibitor, argatroban, using a local drug delivery device would prevent restenosis after plain old balloon angioplasty (POBA). METHODS AND RESULTS: Seventy patients with chronic coronary artery disease requiring POBA were randomly assigned to wither the control group (n=35) or the argatroban group (n=35). In the argatroban group, argatroban was administered intravenously for 30 min before the POBA and intracoronarily into the dilated site using a Dispatch catheter immediately after the POBA, followed by a postoperative intravenous infusion for 4 h. The angiographical lesion restenosis and clinical restenosis rates at follow-up were significantly lower in the argatroban group (27% and 14%) than in the control group (56% and 37%; p=0.02 and p=0.03, respectively). There was no major complication during the procedure. CONCLUSION: The local delivery of argatroban is safe and effective in preventing restenosis after balloon angioplasty.

Aged↗

Reduced oxygen uptake increase to work rate increment (DeltaVO2/DeltaWR) is predictable by VO2 response to constant work rate exercise in patients with chronic heart failure.

Patients with reduced peak oxygen uptake (VO2) due to chronic heart failure (CHF) exhibit abnormal VO2 kinetics even during mild to moderate exercise. This is characterized by a reduced ratio of the VO2 increase to the work rate increment (DeltaVO2/DeltaWR) during ramp exercise, and by a slow increase in VO2 during constant work rate exercise. Because the slow kinetics alone is unlikely to explain the reduced DeltaVO2/DeltaWR on theoretical grounds, we can postulate that the linearity between work rate and VO2 may be impaired when exercise is imposed in a ramp fashion. The present study was designed to address this issue. In 21 CHF patients and 17 normal controls, we performed both symptom-limited exercise testing (15 W. min(-1) ramp) and a constant work rate exercise test (0 W followed by 50-W step). The VO2 step response was used to mathematically derive the hypothetical VO2 ramp response by time integration. Although peak VO2 and work rate were both significantly lower in patients, the attenuation in peak VO2 was more prominent ( p<0.05), which could be explained by a lower DeltaVO2/DeltaWR in patients compared with controls [8.1 (SD 1.0) and 9.8 (0.5) ml. min(-1). W(-1), p<0.01]. The hypothetical DeltaVO2/DeltaWR derived from the VO2 step response was also significantly lower in patients [8.7 (1.0) and 10.0 (0.7) ml. min(-1). W(-1), p<0.01]. The hypothetical and measured DeltaVO2/DeltaWR were highly correlated ( r=0.78, p<0.001). Thus, we can reasonably predict the VO2 ramp response from the VO2 response to a step increase in work rate, indicating that linearity between VO2 and work rate is held constant irrespective of loading patterns. Additional studies, such as those including evaluation of anaerobic bioenergetics, are needed to further elucidate the precise mechanism(s) of this phenomenon.

Chronic Disease↗

Patients with large myocardial infarction gain a greater improvement in exercise capacity after exercise training than those with small to medium infarction.

BACKGROUND: It remains unclear whether patients with large-size myocardial infarction (MI) achieve the same benefit from exercise training as do those with small- to medium-size MI. HYPOTHESIS: This study was designed to determine the magnitude and mechanisms underlying improvement in exercise capacity in patients with large-size MI after cardiac rehabilitation. METHODS: In all, 296 patients who participated in a cardiac rehabilitation program after acute MI were divided into two groups according to the peak serum creatine phosphokinase (CPK) level: the group with large infarction (Group 1) (> or = 5000 U/l peak CPK, 64 patients) and the group with less extensive infarction (Group 2) (< 5000 U/I, 232 patients). Exercise capacity was assessed before and after a 3-month cardiac rehabilitation program that included exercise training. RESULTS: Before exercise training, both the peak work rate (p < 0.05) and peak oxygen uptake (VO2) (p < 0.01) were significantly lower in Group 1 than in Group 2. After exercise training, the changes in peak work rate and peak VO2 were significantly greater in Group 1 than in Group 2 (both p < 0.01). The infarction size measured by the peak CPK level correlated significantly with both the baseline exercise capacity and its improvement after exercise training, although these correlations were insignificant in a multivariate analysis. In the multivariate analysis, the improvement in exercise capacity is determined by age and baseline exercise capacity, which is determined by the duration of inactivity, minute ventilation (VE)/VCO2 slope and left ventricular end-diastolic pressure. CONCLUSIONS: Compared with patients with small- to medium-size myocardial infarction, patients with large infarction gain a greater improvement in exercise capacity after exercise training due to reversal of physical deconditioning and improvement in congestive heart failure.

Adaptation, Physiological↗

Exercise training without ventricular remodeling in patients with moderate to severe left ventricular dysfunction early after acute myocardial infarction.

BACKGROUND: The purpose of this study was to determine whether or not patients with moderate to severe left ventricular (LV) dysfunction benefit from exercise training starting early after acute myocardial infarction (AMI) without deteriorating LV remodeling. METHODS: We investigated changes in exercise capacity and LV end-diastolic dimension (LVDd by two-dimensional echocardiography) before and after exercise training in 126 patients after AMI. Patients were divided into three groups according to LV ejection fraction (EF) at the beginning of exercise training: 74 patients with LVEF>/=45% (Group H), 35 patients with 35%</=LVEF<45% (Group M), and 17 patients with LVEF<35% (Group L). Exercise training was prescribed at a moderate intensity (50-60% of heart rate reserve or Karvonen's equation). Exercise capacity was assessed by peak work rate (WR) and peak oxygen uptake (VO(2)) by upright cardiopulmonary exercise test before and after 3 months of exercise training. LVDd was measured before and at 27+/-10 months of follow-up period. RESULTS: At the baseline, Group L had a significantly lower LVEF (H 55+/-7 vs. M 40+/-3 vs. L 30+/-3%, P<0.05), significantly greater LVDd (49+/-6 vs. 52+/-7 vs. 56+/-6 mm, P<0.05), and a higher incidence of anterior infarction (P<0.01) compared with Groups H and M, whereas there were no difference in age, sex, coronary risk factors, the incidence of multivessel disease, prior myocardial infarction, peak WR or peak VO(2) among the three groups. After 3 months of exercise training, exercise capacity increased significantly (all P<0.01) in all groups. The magnitudes of the increases in peak VO(2) (%Deltapeak VO(2): 18+/-20 vs. 15+/-19 vs. 18+/-17%, NS) and peak WR (%Deltapeak WR: 17+/-17 vs. 16+/-14 vs. 15+/-13%, NS) were similar among the three groups. In addition, there was no significant correlation between %Deltapeak VO(2) and baseline LVEF. No increase in LVDd was observed in any group at follow-up (H 48+/-5 to 49+/-4 mm vs. M 53+/-8 to 52+/-8 mm vs. L 57+/-5 to 57+/-7 mm, NS in each group). CONCLUSION: Patients with moderate to severe LV dysfunction benefit from exercise training starting early after AMI without deteriorating LV remodeling, with a similar magnitude of improvement in exercise capacity to that in patients with mild LV dysfunction.

Adult↗

Lesion severity and hypercholesterolemia determine long-term prognosis of vasospastic angina treated with calcium channel antagonists.

Although patients with medically treated vasospastic angina have a good outcome, few data exist regarding the role of underlying lesion severity associated with or without hyperlipidemia in the prognosis. Therefore, the aim of the present study was to assess the relationship between the long-term outcome of vasospastic angina and the factors influencing its prognosis. A total of 256 patients (219 men, 37 women; mean age, 54.1+/-9.2) who had coronary spasm with or without underlying lesions and were being treated with calcium channel antagonists were enrolled and followed for 13.6+/-3.7 years. Cardiac events consisted of cardiac death and ischemic events, which included acute myocardial infarction and unstable angina. Cox analysis selected coronary artery stenosis (CAS, >/=50%) and risk factors such as age, hypertension, diabetes mellitus, low-density lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The presence of significant CAS was an independent predictor of event-free survival (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In 193 patients without significant CAS, there were 10 cases of cardiac death (5.2%, p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6, p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free survival in patients with than in those without lesions (p<0.0001 by log-rank test). These results demonstrate that the most important factor for long-term prognosis of vasospastic angina treated with calcium channel antagonists is significant CAS. High LDL-C, which might alter the underlying coronary endothelial function and/or accelerate atherosclerotic lesions, could also contribute to the occurrence of cardiac events, particularly in patients without significant CAS.

Angina Pectoris↗

Use of exercise cardiac rehabilitation after acute myocardial infarction.

The purpose of this study was to determine the rate of participation of patients after acute myocardial infarction (AMI) in phase II cardiac rehabilitation with exercise training (ie, exercise cardiac rehabilitation, ECR) in Japan. Forty-six hospitals treating patients with AMI were surveyed for their implementation of phase II ECR after AMI in 1996-98. Of the 46 hospitals, 19 were approved and 27 were not approved for health insurance payment for ECR. A total of 13685 patients with AMI were admitted to the 46 hospitals. There were no differences between approved and non-approved hospitals in the annual number of patients with AMI (Approved, 117+61 vs Non-approved, 86+71 patients per hospital, NS), the rate of performance of emergency coronary angioplasty (63+16 vs 65+20%, NS), or the rate of emergency coronary stenting (31+16 vs 34+22%, NS). However, ECR was performed routinely in 84.2% (16/19 hospitals) of the approved hospitals, but in only 22.2% (6/27 hospitals) of the non-approved hospitals (p<0.001). Although the participation rate of AMI patients in ECR was 21.0% (2875/13685 patients) overall, it was markedly lower in the non-approved hospitals (8.0%, 557/6999 patients) than in the approved hospitals (34.7%, 2318/6686 patients, p<0.0001). Based on the present result, the overall rate of participation of AMI patients in ECR in Japan was estimated at 4.8-11.7%. Despite similar patient volumes and acute phase interventional treatment of AMI between the hospitals approved and not approved for health insurance payment for ECR, ECR was markedly underused in the non-approved hospitals in Japan. To promote ECR for all AMI patients in Japan, the number of hospitals approved for ECR should be substantially increased.

Economics, Hospital↗

[Exercise therapy for chronic heart failure].

Increased mortality and impaired exercise tolerance is the two major clinical problems in patients with chronic heart failure(CHF). In addition, for many years, bed rest has been recommended for patients with CHF. However, in the last decade, exercise training has been shown to improve exercise capacity, quality of life, and event-free survival in patients with CHF. Furthermore, exercise training improves autonomic nerve function and vascular endothelial function in these patients. Based on these lines of evidence, clinical practice guidelines of exercise therapy for CHF have recently been published. More effort should be made to establish the optimal exercise prescription and to increase the implementation of exercise training as a non-pharmacologic therapy for CHF.

Autonomic Pathways↗

Continuous milrinone infusion during preoperative anti-inflammatory therapy in inflammatory aortic aneurysm complicating severe congestive heart failure.

We report a 48-year-old man with inflammatory aortic aneurysm in the ascending aorta complicating severe heart failure due to massive aortic regurgitation. Continuous intravenous milrinone infusion was highly effective in reducing pulmonary arterial pressure and improving subjective symptoms during preoperative anti-inflammatory corticosteroid therapy over 7 weeks without any adverse effects or tolerance. Bentall's operation with a valved conduit was successfully performed after complete stabilization of inflammatory markers, and then milrinone was tapered off uneventfully. We consider that continuous milrinone infusion may be suitable for patients with surgically correctable inflammatory cardiovascular diseases complicating severe heart failure in whom maintenance of optimal hemodynamics is necessary for several weeks during preoperative anti-inflammatory corticosteroid therapy.

Adrenal Cortex Hormones↗

Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes.

Single-nucleotide polymorphisms (SNPs) located in coding regions (coding SNPs; cSNPs) with amino acid substitution can potentially alter protein function. Therefore, identification of the nonsynonymous cSNPs of the genes of common diseases is valuable in tests of association with phenotypes. In this study, we validated 525 candidate cSNPs from 179 hypertension candidate genes deposited in the publicly available database dbSNP by DNA sequencing of samples from 32 Japanese individuals. We identified a total of 143 SNPs (27%) in 93 hypertension candidate genes. We also identified 16 new SNPs, for a total of 159 SNPs. Of the 159 SNPs thus identified, 104 were nonsynonymous. We estimate that approximately 20% of the SNPs deposited in dbSNP database showed a minor allele frequency of over 5%. The candidate SNPs for hypertension identified in this study would be valuable for association studies with hypertension to accelerate the identification of hypertension genes.

Gene Frequency↗

Intravenous adrenomedullin in myocardial function and energy metabolism in patients after myocardial infarction.

This study investigated the effects of adrenomedullin on left ventricular myocardial contraction and relaxation, coronary blood flow, and myocardial oxygen consumption in comparison with those of atrial natriuretic peptide (ANP). Fourteen patients who had had myocardial infarctions were randomly assigned to receive IV infusion of adrenomedullin (0.05 microg/kg/min) or ANP (0.05 microg/kg/min). Both adrenomedullin and ANP significantly decreased left ventricular systolic pressure (-17 mm Hg, -13 mm Hg, respectively, both p < 0.05). The increase in cardiac index by adrenomedullin (+31%) was significantly greater than that by ANP (+16%). Adrenomedullin significantly increased an index of myocardial contractility, Emax (2.5 +/- 0.3 mm Hg-3.7 +/- 0.3 mm Hg/ml, p < 0.05) and shortened an index of myocardial relaxation, Tau (52 +/- 5 ms-48 +/- 4 ms, p < 0.05). In contrast, ANP did not significantly alter either parameter. In addition, adrenomedullin, but not ANP, significantly increased coronary sinus blood flow (73 +/- 10 ml/min-86 +/- 10 ml/min, p < 0.05). Adrenomedullin did not increase myocardial oxygen consumption. Unlike ANP, IV administration of adrenomedullin enhanced left ventricular myocardial contraction and improved left ventricular relaxation without increasing myocardial oxygen consumption in patients who had had a myocardial infarction.

Adrenomedullin↗

O2 extraction during exercise determines training effect after cardiac rehabilitation in myocardial infarction.

Correlations between baseline hemodynamic and oximetric variables during an invasive exercise test and an improvement in peak oxygen uptake (peak VO2) after exercise training (ET) were examined in 20 patients who participated in a cardiac rehabilitation program after acute myocardial infarction (AMI). Peak VO2 significantly increased by 23 +/- 21% (p < 0.01) after ET and the improvement best correlated with the change in O2 extraction fraction ([arterial O2 content-venous O2 content]/arterial O2 content) during an exercise testbefore ET (r = -0.61, p<0.01). Exercise capacity was improved to a greater extent by ET in patients with a smaller increase in O2 extraction fraction during an exercise test before ET. Thus, O2 extraction fraction during an exercise test before ET may be a useful predictor of the improvement in exercise capacity after ET in post-AMI patients.

Aged↗

Safety and implementation of exercise testing and training after coronary stenting in patients with acute myocardial infarction.

The purpose of this study was to determine the incidence of subacute stent thrombosis related to exercise testing (ETT) or exercise training in cardiac rehabilitation (exercise cardiac rehabilitation (ECR)) and to clarify the appropriate timing of ETT and ECR in patients with acute myocardial infarction (AMI) treated with coronary stenting, because the safety and appropriate timing of ETT and ECR after coronary stenting for AMI have not been established. Forty-six institutes performing emergency percutaneous coronary intervention (PCI) for AMI were surveyed for the incidence of exercise-related subacute stent thrombosis and the timing of the start of ETT and ECR in patients with AMI in 1996-1998. Among the total 13,685 patients with AMI, 4,360 (31.9%) underwent coronary stenting. Of the 132 (3.0%) subacute stent thromboses that developed within 1 month after stenting, only one event was related to maximal ETT and occurred in a patient not receiving ticlopidine. No stent thrombosis occurred in association with submaximal ETT or ECR. In 7 institutes, maximal ETT was routinely performed at 14 days after stenting for AMI without any adverse events, and in 6 institutes, ECR was routinely started within 7 days without any adverse events. This survey found that only 21.0% of all AMI patients participated in ECR. In conclusion, subacute stent thrombosis related to ETT or ECR is extremely rare (0-0.02%) in patients with AMI, especially when they are receiving ticlopidine, and therefore ETT and ECR for stented patients with AMI need not be delayed (ie, approximately 7 days after stenting for submaximal ETT and ECR, and 14 days after stenting for maximal ETT). The rate of participation of post-AMI patients in ECR is low in Japan, even in major hospitals that are actively working in the field.

Data Collection↗