An association analysis between genetic polymorphisms of matrix metalloproteinase-3 and methylenetetrahydrofolate reductase and myocardial infarction in Japanese.
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Biomedical subjects
Publications and source records attributed to H Nonogi.
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The appearance of serum troponin T (tn-T) on day 1 after acute myocardial infarction (AMI) strongly depends on coronary reperfusion. In contrast, the kinetics of tn-T release after day 1 after AMI are unaffected by the reperfusion status, and reflect the degradation of myofilaments in irreversibly damaged cells. However, it is not known whether serum tn-T levels after day 1 after AMI can be used to predict the long-term outcome. The purpose of this study was to elucidate the prognostic value of determining the tn-T level on day 3 or 4 after AMI. Serum tn-T levels on day 3 or 4 after AMI were measured in 121 patients (92 men and 29 women, mean age 65 years). Mean follow-up period was 526 days. There were 12 deaths (9 cardiac and 3 noncardiac) during the follow-up period. By Kaplan-Meier analysis, patients with tn-T levels higher than the median level (6.9 ng/ml) had a significantly higher mortality rate than those with submedian levels (p <0.01). By multivariate Cox proportional-hazards regression analysis, the serum tn-T level was an independent predictor of the long-term outcome after AMI (p <0.01). Futhermore, in patients with a first AMI, the serum tn-T level exhibited a significant negative linear correlation with left ventricular ejection fraction assessed 4 weeks after AMI (r = -0.48, p <0.001). Increased serum tn-T levels on day 3 or 4 after AMI are a powerful noninvasive predictor of poor long-term prognosis, reflecting residual left ventricular function after AMI.
The antiproliferative activity of alkylated heparin, in which the terminal end of heparin is derivatized with an alkyl group (butyl, octyl, lauryl, stearyl), was examined using vascular smooth muscle cells. The proliferation of cells, which were growth-arrested prior to addition of heparin, was inhibited in proportion to both increase in the chain length of the alkyl group of alkylated heparin and alkylated heparin concentration in the serum-containing medium. The antiproliferative activity of stearyl group derivatized heparin was significantly stronger than that of nonmodified heparin. Little proliferation was observed at high dose (500 microg/mL). Confocal laser scanning microscopic observation indicated that alkylated heparin was accumulated on the cell membranes at an early incubation time, followed by homogeneous distribution of intracellular space. The therapeutic potential of alkylated heparin for preventing restenosis after balloon angioplasty is discussed.
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Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.
The TAMI-6 trial has demonstrated that coronary reperfusion >6h after onset (ie, late reperfusion) in patients with acute myocardial infarction (AMI) does not improve left ventricular (LV) function during the chronic phase of infarction. However, the low patency rate (only 60%) of the infarct-related artery (IRA) during the chronic phase in the TAMI-6 trial raises a new hypothesis that late reperfusion with a higher patency rate may improve LV function during the chronic phase. Forty-four patients with AMI, who were admitted to hospital 6-24h after the symptom onset and in whom emergency coronary angiography revealed a total occlusion of the IRA, were randomly assigned to either the late reperfusion group (n=22) or the non-reperfusion group (n=22). The initial success rate of reperfusion therapy in the late reperfusion group was 86% and the chronic patency rate of the IRA was 91%. The improvements in ejection fraction and chord shortening in the infarct region from the acute phase to the chronic phase were significantly greater in the late reperfusion group than in the non-reperfusion group. Late reperfusion with a high patency rate of the IRA significantly improves LV global and regional function in patients with AMI.
The present study determined the white blood cell (WBC) count and the serum C-reactive protein (CRP) level in 27 patients with coronary spastic angina, 16 with Braunwald class IB unstable angina (UA) and 13 with Braunwald class IIIB. The relationship between the clinical presentation of UA and the requirement for emergency percutaneous transluminal coronary angioplasty (PTCA) was examined, and in patients with medically refractory angina, the determining factor among the clinical manifestations of angina was also investigated. In the acute phase, the WBC count and the serum CRP level were significantly higher in patients with Braunwald class IIIB than in those with coronary spastic angina or Braunwald class IB UA (p<0.001). In the Braunwald class IIIB group, a significantly higher rate of patients required emergency PTCA than that of the coronary spastic angina group (p<0.01). Patients with medically refractory angina had a significantly higher WBC count and higher serum CRP level on admission, and the WBC count on admission was independently associated with medically refractory angina by multivariate analysis (p<0.05). Inflammation may play a major pathological role in the rapid development of acute coronary syndrome.
Nifekalant hydrocholoride, a novel class III antiarrhythmic agent, was used as the treatment in 4 patients with extensive anterior infarction and severe ventricular dysfunction. The malignant ventricular tachyarrhythmia was effectively suppressed at a relatively low dose, without compromising the hemodynamics, indicating that this potent K+ channel blocker has therapeutic potential for acute myocardial infarction.
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BACKGROUND: Previous studies have shown that repeated systemic administration of human recombinant hepatocyte growth factor (hrHGF) in mg/kg levels modulates the wound-healing process in various diseases. Recently, HGF has been characterized as one of the most potent endothelial-cell-specific growth factors. We tested our hypothesis that local delivery of hrHGF, even at low microg/kg levels (> or =2 orders of magnitude lower than systemically administered doses), might attenuate neointimal hyperplasia in response to vascular injury via accelerated reendothelialization. METHODS AND RESULTS: The iliac artery was denuded in 16 New Zealand White rabbits (3 kg), followed by administration, via a drug delivery catheter, of either hrHGF (10 microg; n = 11) or control vehicle (n=5) over 20 minutes. In pilot studies using this device, the drug permeated into the medial tissues, where it persisted for > or =24 hours. Four weeks after the local delivery of hrHGF, computer-assisted morphometric analysis revealed significant reduction in the intimal area (hrHGF, 0.37+/-0.21 versus control, 0.68+/-0.16 mm(2), mean +/- SD; P<0.05) but no change in the medial area (hrHGF, 1.03+/-0.21 versus control, 1.10+/-0.52 mm(2)). Scanning electron microscopy revealed extensive endothelialization with regular and confluent endothelial cell layer regeneration in the hrHGF-treated vessels. CONCLUSIONS: Accelerated endothelialization after local delivery of hrHGF, a novel and potent endothelial cell mitogen, effectively attenuates neointimal proliferation even after single low-dose administration. This observation could have potential therapeutic implications in the prevention of restenosis after angioplasty.
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This study was conducted to assess the determinants of the procedural success and long-term clinical benefits of percutaneous transluminal balloon angioplasty (PTCA) of chronic total occlusion (CTO) in recent years. Two hundred and twenty-six consecutive patients who underwent PTCA of CTO were divided into two groups according to the procedural success (n = 134) or failure (n = 92). Both groups were analyzed in terms of the initial success, predictors of procedural failure, and clinical outcome. The procedural success rate was noted to have improved to more than 70% since 1995. A multiple logistic regression analysis revealed that the presence of calcification, the length of the occlusion and the presence of multivessel disease were independent predictors of procedural failure. Cardiac death and the need for coronary surgery were significantly less frequent in patients with procedural success than in those with procedural failure. In properly selected cases, the success rate of PTCA of CTO is acceptable. Long-term clinical benefit is suggested by the high rate of freedom from coronary surgery and the low cardiac death rate in the patients who underwent successful revascularization.
Serial improvement in myocardial perfusion images from the acute or subacute to the chronic stage of acute myocardial infarction (AMI) has been attributed to improved coronary microcirculation or cell function after acute ischaemia and reperfusion. However, conventionally used non-gated imaging cannot eliminate the effect of improved regional contraction. We studied the possibility that such scintigraphic improvement reflects the functional recovery by using ECG-gated myocardial perfusion imaging with technetium-99m sestamibi. Nineteen AMI patients who received acute reperfusion therapy underwent ECG-gated myocardial single-photon emission tomography (SPET) in the subacute and chronic stages. Serial changes in regional image count distributions were analysed on the non-gated, end-diastolic (ED) and end-systolic (ES) images by using segmental mean percent peak activity (MPA) and AMPA (MPA in chronic stage - MPA in subacute stage) on bull's-eye polar maps. These changes were compared with those in regional wall motion on biplane left ventriculography (LVG) from the acute (just after reperfusion) to the chronic stage. During the follow-up, regional wall motion remained the same in 42 (group A) but improved in 17 (group B) of the 59 ischaemically compromised segments. MPA showed no improvement in group A but significant improvement in group B on the non-gated and ES images (P<0.0001 and P<0.001, respectively). However, MPA on the ED images showed no improvement in either group. In the follow-up study of AMI, the scintigraphic improvement documented on the non-gated myocardial images appears to be mainly related to the recovery of wall thickening and not to a real improvement in myocardial perfusion. Therefore, ECG-gated myocardial imaging, which enables simultaneous assessment of changes in perfusion and contraction, is preferable to conventional non-gated imaging for follow-up of AMI.
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OBJECTIVES: We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI). BACKGROUND: The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion. METHODS: We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS: The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001) and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS: Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.