ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background - The usefulness of adriamycin (ADR), potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy and congestive heart failure. Subcellular changes leading to heart failure are suggested to be mediated by a drug-induced increase in free radicals and lipid peroxidation. In an earlier study, concurrent treatment with probucol (PROB), a lipid-lowering drug with strong antioxidant properties, was shown to offer only partial protection against ADR cardiomyopathy. The present study had two aims: to determine whether this protective effect can be improved further by extended treatment with PROB, and to determine whether PROB affects the antitumor properties of ADR.Methods and Results - ADR (cumulative dose, 15 mg/kg body wt) was administered in rats in six equal injections (IP) over a period of 2 weeks. Three weeks after the end of treatment, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage. Myocardial glutathione peroxidase (GSHPx) activity was decreased and lipid peroxidation was increased. Administration of PROB (cumulative dose, 120 mg/kg body wt) in 12 equal injections (IP), before and concurrent with ADR, completely prevented these cardiomyopathic changes, normalized left ventricular function, lowered mortality, and eliminated ascites. Treatment with PROB was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities with a concomitant decrease in lipid peroxidation. Tumor regression in syngeneic DBA/2 mice inoculated with L5178Y-F9 lymphoma cells in the ADR+PROB group was significant and comparable to the ADR group.Conclusions - These data show for the first time that PROB can provide complete protection against ADR cardiomyopathy without interfering with antitumor properties of the drug. This protective effect of PROB may be related to the maintenance of the antioxidant status of the heart. (Circulation. 1995;91:10-15).

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Angiotensin-converting enzyme (ACE) inhibitors show major differences in their affinity for cardiac and other tissue ACEs, and their effects on tissue ACE range from minimal to nearly complete blockade. Angiotensin II taken up from the circulation or generated in the heart may mediate the cardiac hypertrophic response to increased cardiac load. Thus, differences between the ACE inhibitors regarding their effects on cardiac ACE may determine their effects on prevention or regression of cardiac hypertrophy.Methods and Results In the present study, we assessed the effects of ACE inhibitors with low (enalapril) and high (quinapril) affinity for cardiac tissue ACE on prevention of volume overload-induced cardiac hypertrophy in relation to their hemodynamic effects. Both blockers were equipotent for circulatory ACE as assessed from the pressure response curve to angiotensin I. Both blockers partially (and similarly) prevented the increase in left ventricular end-diastolic pressure by aortocaval shunt. However, only quinapril prevented or attenuated the development of right ventricular hypertrophy and left ventricular hypertrophy and dilation.Conclusions The present findings further stress the involvement of the renin-angiotensin system as a trophic stimulus in the development of cardiac hypertrophy in this model. Moreover, the low affinity of enalapril for cardiac ACE appears to lead to continuous angiotensin II generation in the heart and can thus explain the failure of enalapril to attenuate hypertrophic response of the heart induced by shunt despite decreasing cardiac volume overload. (Circulation. 1995;91:16-19.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Inflammatory reactions have an important part in atherosclerosis. Smooth muscle cells, endothelial cells, monocytes, and T lymphocytes are actively involved. The purpose of this study was to assess whether T lymphocytes are activated in patients with stable angina pectoris who are candidates for a percutaneous transluminal coronary angioplasty (PTCA) and the influence of PTCA on this process.Methods and Results Twenty-four patients participated in the study. All were 40- to 60-year-old men, and all but one underwent successful PTCA. Blood samples were taken 1 day before PTCA and 1 week, 1 month, and 2 months after. Two groups of patients were detected: group A, 11 patients who had high levels of soluble interleukin-2 receptor (sIL-2R) before PTCA that decreased toward normal during the follow-up period in most of them; and group B, 13 patients who did not have elevated sIL-2R levels before PTCA and in whom sIL-2R levels did not change after the procedure. Group C consisted of 15 healthy men whose sIL-2R levels were in the normal range (control subjects).Conclusions (1) T lymphocytes are activated in stable angina patients. (2) The level of sIL-2R can be a reliable laboratory marker for follow-up of patients after PTCA, especially those with high sIL-2R levels before the procedure. (Circulation. 1995;91:20-22.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Data concerning the relation between anti-phospholipid (aPL) antibodies and myocardial infarction in subjects without evidence of overt autoimmune disease are conflicting. All published studies have been performed on survivors of myocardial infarction or in patients with established coronary heart disease. The purpose of the present study was to determine whether the presence of aPL antibodies, namely, anti-cardiolipin (aCL) antibodies, carries a risk for myocardial infarction in a prospective cohort.Methods and Results The sera to be studied were drawn at entry from middle-aged dyslipidemic men (non-high-density lipoprotein cholesterol, G5.2 mmol/L) participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil. Samples were tested for IgG-class antibodies to cardiolipin by an ELISA. The risk was estimated with logistic regression analysis using a nested case-control design with 133 patients (myocardial infarction or cardiac death) and 133 control subjects, matched for treatment (gemfibrozil/placebo) and geographical area. The aCL antibody level, as expressed in optical density units, was significantly higher in patients than in control subjects (0.417 versus 0.361; P<.005). Subjects with the antibody level in the highest quartile of distribution had a relative risk for myocardial infarction of 2.0 (95% confidence interval, 1.1 to 3.5) compared with the remainder of the population. This risk was independent of confounding factors, such as age, smoking, systolic blood pressure, low-density lipoprotein (LDL), and high-density lipoprotein. There was a correlation between the levels of aCL antibodies and antibodies to oxidized LDL (r=.40, P<.001), and their joint effect was additive for the risk.Conclusions In a prospective cohort of healthy middle-aged men, the presence of a high aCL antibody level is an independent risk factor for myocardial infarction or cardiac death. Antibodies to cardiolipin and oxidized LDL may, at least in part, represent cross-reactive antibody populations. (Circulation. 1995;91:23-27)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Thrombin activity increases in patients treated with coronary thrombolysis for acute myocardial infarction, but the mechanisms are not well defined. We have shown that thrombin activity increases in plasma and whole blood incubated with plasminogen activators and appears to be plasmin mediated and dependent on activity of the factor VIIIa/IXa complex.Methods and Results In the present study, increases in thrombin activity induced by incubation of recalcified citrated plasma with 0.16 to 0.5 mol/L plasmin at 37 degrees C were markedly attenuated in recalcified citrated plasma deficient in factors XI or XII, prekallikrein, or high molecular weight kininogen, as well as in plasma incubated with plasmin in the presence of 3.5 mol/L corn trypsin inhibitor, a specific factor XIIa inhibitor. Increases in thrombin activity also occurred in nonanticoagulated whole blood incubated with pharmacological concentrations of plasminogen activators and were markedly attenuated in the presence of corn trypsin inhibitor. Plasmin-mediated (0.25 mol/L) activation of purified factor XII occurred in 0.05 mol/L Tris-HCl and 0.012 mol/L NaCl (pH 7.8) at 37 degrees C, resulting in equimolar quantities of two fragments that corresponded to cleavage of factor XII at Arg353-Val354, the site involved in kallikrein-mediated activation of factor XII, and cleavage at Lys346-Ser347, an apparently novel site of plasmin-mediated hydrolysis of factor XII. Contact activation was also demonstrated in plasma samples from patients after treatment with fibrinolytic agents for myocardial infarction, by demonstrating cleavage of high molecular weight kininogen from its one-chain to its two-chain form by ligand blotting with Iodine-125-prekallikrein.Conclusions Plasmin-mediated activation of the contact system of coagulation appears to account, at least in part, for increases in procoagulant activity in patients treated with fibrinolytic agents. It may also explain hypotension, by release of bradykinin from high molecular weight kininogen, and complement activation, by activated factor XII, that has been demonstrated in these patients. (Circulation. 1995;91:28-36.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Ischemic preconditioning has been shown to reduce myocardial infarct size in experimental models, but its role in patients remains unclear. Angina before myocardial infarction reflects brief episodes of ischemia and may be a marker of preconditioning. As part of the Thrombolysis in Myocardial Infarction (TIMI) 4 study, we performed an analysis on the effect of a history of previous angina on in-hospital outcomes for patients with acute myocardial infarction.Methods and Results Patients eligible for thrombolytic therapy were enrolled into the study. Data were collected from case report forms regarding previous history of angina, in-hospital outcome and 6-week follow-up. Two hundred eighteen patients had a history of previous angina at any time before acute myocardial infarction, and 198 patients did not have previous angina. Patients with any previous history of angina were less likely than with those without angina to experience in-hospital death (3% versus 8%) (P=.03), severe congestive heart failure (CHF) or shock (1% versus 7%, P=.006), or the combined end point of in-hospital death, severe CHF, or shock (4% versus 12%, P=.004). Moreover, patients with any history of angina were more likely to have a smaller creatine kinase (CK)-determined infarct size (119 versus 154 CK integrated units; P=.01) and were less likely to have Q waves on their ECG (57% versus 69%; P=.01). In the subset of patients who experienced angina within the 48 hours before infarction (compared with those who did not), there was a trend toward less likely in-hospital death (3% versus 6%; P=.09), a lower incidence of severe CHF or shock (1% versus 6% P=.008), a lower combined end point of death, CHF, or shock (3% versus 10%; P=.006), smaller infarct size assessed by CK (115 versus 151 CK units; P=.03), and a trend toward fewer Q-wave infarcts. However, patients with a history of previous angina did have a trend toward more recurrent ischemic pain. Of importance is that the beneficial in-hospital effects of previous angina were not dependent on angiographically visible coronary collaterals.Conclusions Previous angina confers a beneficial effect on in-hospital outcome after acute myocardial infarction. The reasons for this benefit are uncertain, but one potential mechanism for this observation may be ischemic preconditioning. (Circulation. 1995;91:37-47.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background Among patients with combined coronary artery and peripheral vascular disease, long-term benefits of surgical therapy compared with medical therapy for coronary artery disease are unknown.Methods and Results Using prospectively collected data from the Coronary Artery Surgery Study registry, we performed a retrospective cohort analysis of 1834 patients (mean age, 56 years; 20% women) with both coronary artery and peripheral vascular disease and evaluated their long-term outcomes. Of these patients, 986 received (nonrandomly) coronary artery bypass graft surgery, and 848 were treated medically. Perioperative mortality was 4.2% (2.9% in the absence of peripheral vascular disease; P=.02). In a mean follow-up period of 10.4 years, 1100 deaths occurred (80% due to cardiovascular causes). For the surgical group, 4-, 8-, 12-, and 16-year estimated probabilities of survival were 88%, 72%, 55%, and 41%, respectively, and 73%, 57%, 44%, and 34%, respectively, for the medical group (P<.0001). Multivariate analysis demonstrated that type of therapy was independently associated with survival (P=.0001;2=15.34). Subgroup analysis suggested that benefits of surgical treatment on survival were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction. Survival free of death or myocardial infarction was also significantly better among the surgical group. Type of therapy was significantly associated with occurrence of late events (P=.01; sup 2 =6.55). Subgroup analysis again demonstrated that beneficial effects of surgery were limited to patients with three-vessel coronary artery disease and were inversely related to ejection fraction.Conclusions Surgical treatment provides long-term benefit for certain subgroups of patients with combined coronary artery and peripheral arterial vascular disease. (Circulation. 1995;91:46-53.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Background To compare cost-effectiveness and utility of four clinical algorithms to diagnose obstructive coronary atherosclerotic heart disease (CAD), we compared exercise ECG (ExECG), stress single photon emission computed tomography (SPECT), positron emission tomography (PET), and coronary angiography.Methods and Results Published data and a straightforward mathematical model based on Bayes' theorem were used to compare strategies. Effectiveness was defined as the number of patients with diagnosed CAD, and utility was defined as the clinical outcome, ie, the number of quality-adjusted life years (QALY) extended by therapy after the diagnosis of CAD. Our model used published values for costs, accuracy, and complication rates of tests. Analysis of the model indicates the following results. (1) The direct cost (fee) for each test differs considerably from total cost per QALY. (2) As pretest likelihood of CAD (pCAD) in the population increases, there is a linear increase in cost per patient tested but a hyperbolic decrease in cost per effect and cost per utility unit, ie, increased cost-effectiveness and decreased cost per utility unit. (3) At pCAD<0.70, analysis of the model indicates that stress PET is the most cost-effective test, with the lowest cost per utility, followed by SPECT, ExECG, and angiography, in that order. (4) Above a threshold value of pCAD of 0.70 (for example, middle-aged men with typical angina), proceeding directly to angiography as the first test showed the lowest cost per effect or utility. This quantitative model has the advantage of estimating a threshold value of pCAD (0.70) at which the rank order of cost-effectiveness and cost per utility unit change. The model also allows substitution of different values for any variable as a way to account for the uncertainties of clinical data, ie, changing costs, test accuracy and risk, etc. This procedure, called sensitivity analysis, showed that the rank order of cost-effectiveness did not change despite changes in several variables.0.70.(Circulation. 1995;91:54-65.)

ISSN:0009-7322    

出版商:OVID    

年代:1995

数据来源: OVID