Search PubMed⌕ Search

Biomedical subjects

H S Mueller

Publications and source records attributed to H S Mueller.

At least 19 recordsLinked to original sources
PubMed1995

Predictors of non-Q-wave acute myocardial infarction in patients with acute ischemic syndromes: an analysis from the Thrombolysis in Myocardial Ischemia (TIMI) III trials.

Among patients with acute ischemic syndromes, patients with non-Q-wave acute myocardial infarction (AMI) are known to be at higher risk for death, reinfarction, and other morbidity than those with unstable angina. The aim of this study was to develop a clinically useful prediction rule to assist in distinguishing, at the time of presentation, patients with non-Q-wave AMI from those with unstable angina. The TIMI IIIB trial enrolled 1,473 patients presenting with ischemic pain at rest within 24 hours who had either electrocardiographic changes or documented coronary artery disease. Non-Q-wave AMI on presentation was documented by elevation of creatine kinase-MB in 33% of patients. Fifty clinical and electrocardiographic variables were compared between the patients with non-Q-wave AMI and unstable angina. After performing logistic regression, 4 baseline characteristics independently predicted non-Q-wave myocardial AMI: the absence of prior coronary angioplasty (odds ratio [OR] = 3.3, p < 0.001), duration of pain > or = 60 minutes (OR = 2.9, p < 0.001), ST-segment deviation on the qualifying electrocardiogram (OR = 2.0, p < 0.001), and recent-onset angina (OR = 1.7, p = 0.002). Using these 4 characteristics, a prediction rule for non-Q-wave AMI was developed. For the entire cohort of patients in TIMI III, the percentages of patients with non-Q-wave AMI when 0, 1, 2, 3, and 4 risk factors were present were 7.0%, 19.6%, 24.4%, 49.9%, and 70.6%, respectively (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Prognostic significance of nonfatal reinfarction during 3-year follow-up: results of the Thrombolysis in Myocardial Infarction (TIMI) phase II clinical trial. The TIMI Investigators.

OBJECTIVES: This study sought to assess the independent contribution of nonfatal reinfarction to the risk of subsequent death in patients with acute myocardial infarction undergoing thrombolytic therapy. BACKGROUND: A composite of "unsatisfactory outcomes" as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infarction. The significance of nonfatal reinfarction as a component of a composite end point has not been evaluated in the thrombolytic era. METHODS: Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in patients with acute myocardial infarction entered into the Thrombolysis in Myocardial Infarction Phase II trial. The independent risk of nonfatal reinfarction for subsequent death within various time intervals of follow-up was determined. The mortality rate after nonfatal reinfarction was compared with that of a matched control group. RESULTS: During 3-year follow-up, 349 of 3,339 patients had a nonfatal reinfarction. Univariate predictors were history (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01), multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter was an independent predictor (relative risk [RR] 1.3, 99% confidence interval [CI] 1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI 1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI 3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6 to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3-year death rate was 14.1% in patients with a nonfatal reinfarction compared with 7.9% (p < 0.01) in a matched control group. Univariate predictors of death after nonfatal reinfarction were age > or = 65 years (p < 0.001), not low risk category (p = 0.015) and history of heart failure before the index event (p < 0.001). Age > or = 65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4). CONCLUSIONS: Nonfatal reinfarction is a strong and independent predictor for subsequent death. It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infarction.

Aged↗
PubMed1994

A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 5 trial.

OBJECTIVES: The purpose of this study was to assess the value of recombinant desulfatohirudin (hirudin) as adjunctive therapy to thrombolysis in acute myocardial infarction. BACKGROUND: Failure to achieve initial reperfusion and reocclusion of the infarct-related artery remain major limitations of thrombolytic therapy despite aggressive regimens of heparin and aspirin. Hirudin, a direct thrombin inhibitor, has been shown in experimental models to enhance thrombolysis and reduce reocclusion. METHODS: The Thrombolysis in Myocardial Infarction (TIMI) 5 trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin, given with front-loaded tissue-type plasminogen activator and aspirin to 246 patients with acute myocardial infarction. Patients received either intravenous heparin or hirudin at one of four ascending doses for 5 days. Patients underwent coronary angiography at 90 min and at 18 to 36 h, unless rescue angioplasty was performed. RESULTS: The primary end point, TIMI grade 3 flow in the infarct-related artery at 90 min and 18 to 36 h without death or reinfarction before the 18- to 36-h catheterization was achieved in 97 (61.8%) of 157 evaluable hirudin-treated patients compared with 39 (49.4%) of 79 evaluable heparin-treated patients (p = 0.07). All four doses of hirudin led to similar findings in the angiographic and clinical end points. At 90 min, TIMI grade 3 flow was present in 105 (64.8%) of 162 hirudin-treated patients compared with 48 (57.1%) of 84 heparin-treated patients (p = NS). Infarct-related artery patency (TIMI grade 2 or 3 flow) was similar in the two groups (82.1% and 78.6%, respectively). At 18 to 36 h, 129 (97.8%) of 132 hirudin-treated patients had a patent infarct-related artery compared with 58 (89.2%) of 65 heparin-treated patients (p = 0.01). Reocclusion by 18 to 36 h occurred in 2 (1.6%) of 123 hirudin-treated patients versus 4 (6.7%) of 60 heparin-treated patients (p = 0.07). Death or reinfarction occurred during the hospital period in 11 (6.8%) of 162 hirudin-treated patients compared with 14 (16.7%) of 84 heparin-treated patients (p = 0.02). Major spontaneous hemorrhage occurred in 1.2% of hirudin-treated patients versus 4.7% of heparin-treated patients (p = 0.09), and major hemorrhage at an instrumented site occurred in 16.3% and 18.6%, respectively (p = NS). CONCLUSIONS: Hirudin is a promising agent compared with heparin as adjunctive therapy with thrombolysis for acute myocardial infarction, and its evaluation in larger trials is warranted.

Adjuvants, Pharmaceutic↗
PubMed1994

Role of intra-aortic counterpulsation in cardiogenic shock and acute myocardial infarction.

IACP has played an important role in the evolution of the therapy of cardiogenic shock. Although IACP has not developed to an independent treatment modality, it is an essential adjunct to facilitate early catheterization and reperfusion strategies. With this combined approach, hospital and long-term survival rates have reached encouraging results. In acute myocardial infarction, IACP may evolve into an intriguing adjunct to thrombolysis and/or PTCA. Preliminary data suggest that IACP might decrease the rate of reocclusion and reinfarction after thrombolysis and/or PTCA and, thus, interrupt the vicious cycle of infarct extension, development of left-ventricular failure and cardiogenic shock. Further research is in progress.

Adult↗
PubMed1993

Laser-induced stimulation of thromboxane B2 synthesis in human blood platelets: role of superoxide radicals.

Exposure of platelet-rich plasma to laser radiation at 3.5 W for 30 seconds reduced the threshold concentrations of adenosine diphosphate and L-epinephrine needed from complete platelet aggregation by 20% to 60% and by 30% to 50%, respectively. The irradiation of platelet-rich plasma with laser also increased the basal level of thromboxane A2 from < 0.5 pmol/10(8) platelets for each second of exposure. In contrast, the exposure of gel-filtered platelets to laser produced no effect on the prostanoid formation. However, the addition of laser-exposed platelet-free plasma to gel-filtered platelets stimulated the synthesis of thromboxane A2 in these cells. The effect of laser was completely blocked by adding superoxide dismutase or catalase to the platelet-rich plasma, indicating that the radiation-induced stimulation of thromboxane A2 production was mediated through the generation of superoxide radicals. Electron microscopic studies indicated that the laser-induced stimulation of thromboxane A2 production in platelet can occur without any noticeable damage in the cellular structure.

Blood Platelets↗
PubMed1993

Two- and three-year results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II clinical trial.

OBJECTIVES: This report describes the survival and reinfarction rates for 2- and 3-year follow-up in the Thrombolysis in Myocardial Infarction (TIMI) Phase II clinical trial. BACKGROUND: Patients enrolled in TIMI II were randomly assigned to an invasive (1,681 patients) or a conservative (1,658 patients) management strategy to follow receipt of intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction. METHODS: Eligibility required presentation within 4h of onset of symptoms and at least 1-mV ST segment elevation in two contiguous electrocardiographic leads. The invasive strategy group underwent cardiac catheterization 18 to 48 h after study entry and, when appropriate, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. In the conservative strategy group these diagnostic and revascularization procedures were reserved for recurrent spontaneous ischemia or ischemia on low level exercise at the time of hospital discharge. RESULTS: Complete 2-year follow-up data are available for 3,187 patients (95.4%). Cumulative life-table rates of death or reinfarction were 17.6% for the invasive strategy group and 17.9% for the conservative strategy group (p = NS) and mortality was 8.9% and 8.7% (p = NS), respectively. Complete data are available for 1,959 (90.1%) of the 2,174 patients enrolled for 3 years. Rates of death or reinfarction were 21.0% for the invasive strategy group with 20.0% for the conservative strategy group (p = NS), with mortality of 11.5% and 11.0% (p = NS), respectively. In this cohort, the mortality was 1.3% in the 2nd year and 1.7% in the 3rd year from study entry. CONCLUSIONS: TIMI II invasive and conservative strategies resulted in similar favorable outcomes after 2 and 3 years. Mortality and reinfarction rates in the two strategies were comparable. Deaths were infrequent in the 2nd and 3rd years from study entry.

Aged↗
PubMed1992

Anistreplase versus alteplase in acute myocardial infarction: comparative effects on left ventricular function, morbidity and 1-day coronary artery patency. The TEAM-3 Investigators.

OBJECTIVES: This double-blind, randomized, multicenter trial was designed to compare the effects of treatment with anistreplase (APSAC) and alteplase (rt-PA) on convalescent left ventricular function, morbidity and coronary artery patency at 1 day in patients with acute myocardial infarction. BACKGROUND: Anistreplase (APSAC) is a new, easily administered thrombolytic agent recently approved for treatment of acute myocardial infarction. Alteplase (rt-PA) is a rapidly acting, relatively fibrin-specific thrombolytic agent that is currently the most widely used agent in the United States. METHODS: Study entry requirements were age less than or equal to 75 years, symptom duration less than or equal to 4 h, ST segment elevation and no contraindications. The two study drugs, APSAC, 30 U/2 to 5 min, and rt-PA, 100 mg/3 h, were each given with aspirin (160 mg/day) and intravenous heparin. Prespecified end points were convalescent left ventricular function (rest/exercise), clinical morbidity and coronary artery patency at 1 day. A total of 325 patients were entered, stratified into groups with anterior (37%) or inferior or other (63%) acute myocardial infarction, randomized to receive APSAC or rt-PA and followed up for 1 month. RESULTS: At entry, patient characteristics in the two groups were balanced. Convalescent ejection fraction at the predischarge study averaged 51.3% in the APSAC group and 54.2% in the rt-PA group (p less than 0.05); at 1 month, ejection fraction averaged 50.2% versus 54.8%, respectively (p less than 0.01). In contrast, ejection fraction showed similar augmentation with exercise at 1 month after APSAC (+4.3% points) and rt-PA (+4.6% points), and exercise times were comparable. Coronary artery patency at 1 day was high and similar in both groups (APSAC 89%, rt-PA 86%). Mortality (APSAC 6.2%, rt-PA 7.9%) and the incidence of other serious clinical events, including stroke, ventricular tachycardia, ventricular fibrillation, heart failure within 1 month, recurrent ischemia and reinfarction were comparable in the two groups; and mechanical interventions were applied with equal frequency. A combined clinical morbidity index was determined and showed a comparable overall outcome for the two treatments. CONCLUSIONS: Convalescent rest ejection fraction was high after both therapies but higher after rt-PA; other clinical outcomes, including exercise function, morbidity index, and 1-day coronary artery patency, were favorable and comparable after APSAC and rt-PA.

Anistreplase↗
PubMed1992

Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II.

BACKGROUND: Thrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate. METHODS AND RESULTS: Clinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p less than 0.001); in the invasive strategy, the mortality rates were similar (6.0% and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conservative strategy (14.8% versus 4.2%, p less than 0.001). Reinfarction was not independently correlated with baseline characteristics except with history of angina (relative risk, 1.9). Mortality was lower in current smokers and ex-smokers versus never-smokers (3.6% and 4.8% versus 8.0%, p less than 0.001). Current smokers had a lower risk profile (p less than 0.001), including age, pulmonary edema/cardiogenic shock, history of hypertension, and diabetes. The rate of reinfarction was lower in current smokers versus ex-smokers and never-smokers (4.6% versus 8.3% and 8.8%, p less than 0.001). "Not current smoker" was an independent correlate with reinfarction (relative risk, 1.9). The coronary anatomy did not differ among the current smokers, ex-smokers, and never-smokers. CONCLUSIONS: The strong independent correlation of pulmonary edema/cardiogenic shock with death suggests that thrombolysis is not sufficient to improve survival in these patients. The higher mortality in patients with versus without prior AMI in the conservative strategy suggests that early catheterization and revascularization of these patients might be beneficial. Conversely, the higher mortality in diabetes without prior AMI in the invasive than in the conservative strategy suggests that early aggressive management might not be suitable in this subgroup except for clinical indications. Reinfarction was not predictable by clinical variables except by history of angina. The finding that "not current smoker" was an independent correlate with reinfarction was unexpected.

Female↗
PubMed1991

Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study.

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.

Adrenergic beta-Antagonists↗
PubMed1991

Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease.

Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets). After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases. Twenty-five percent of the patients did not respond to the stimulatory effect of insulin. The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) [insulin-treated] platelets versus 16.35 +/- 2.91 pmol/10(8) [control] platelets) and in patients with acute ischemic heart disease (23.87 +/- 4.1 pmol/10(8) [insulin-treated] platelets versus 7.70 +/- 2.0 pmol/10(8) [control] platelets) by the prostanoid (1.0 microM). The treatment of platelet-rich plasma with the hormone decreased the minimum inhibitory concentration of the prostanoid from 34 +/- 14 to 15 +/- 9 nM (p less than 0.001) in the case of normal volunteers and from 49 +/- 15 to 32 +/- 11 nM (p = 0.002) in the case of "responder" patients. Insulin did not produce any effect on the inhibition of platelet aggregation by the prostaglandin in "nonresponder" patients. In the follow-up study, although the stimulatory effects of insulin on platelets from responder patients were improved to normal levels, the platelets from the nonresponder patients remained persistently unresponsive to the effect of the hormone.

Acute Disease↗
PubMed1990

Reperfusion therapy in acute myocardial infarction: present status and controversy.

Coronary thrombolysis revolutionized the treatment of acute myocardial infarction. Most of the experience was obtained with intravenous use of streptokinase and tissue-type plasminogen activator, the latter being superior to streptokinase in regard to coronary recanalization. Numerous other promising thrombolytic agents are being investigated. Both streptokinase and tissue-type plasminogen activator decreased mortality in large trials; comparison studies in terms of efficacy are presently being performed (GISSI 2). Aspirin is an important adjunct to thrombolytic therapy; it decreased mortality by itself (ISIS 2). Heparin is conventionally used together with thrombolysis. Its efficacy is under study (GISSI 2). Intracranial hemorrhage is the most devastating complication of thrombolysis. With the present dosage regimens, the incidence is approximately 0.5%. Percutaneous transluminal coronary angioplasty in conjunction with thrombolysis accomplished frequent and persistent recanalization of the infarct artery with low mortality, including high risk patients. The TIMI IIB study demonstrated that the results of a "conservative strategy" with aggressive management of recurrent ischemic events were comparable to those of an "invasive strategy." Subgroup analysis should, however, be awaited. High risk patients with low ejection fraction or with shock benefit by early mechanical coronary recanalization. The role of thrombolysis in the "late" stage of transmural myocardial infarction or in the acute ischemic syndrome (unstable angina/non-Q-wave myocardial infarction) is unclear and presently under investigation.

Clinical Trials as Topic↗
PubMed1990

Thrombolysis in Myocardial Infarction (TIMI) phase II trial: outcome comparison of a "conservative strategy" in community versus tertiary hospitals. The TIMI Research Group.

In the conservative strategy arm of phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial, 1,461 patients were treated with intravenous recombinant tissue-type plasminogen activator (rt-PA). Coronary angiography, with angioplasty if feasible, was to be performed only for recurrent spontaneous or exercise-induced ischemia. In this study results in patients treated by this strategy in community and tertiary hospitals are compared. Despite similar baseline findings in the two groups, coronary angiography was performed within 42 days in more patients (542 [48%] of 1,155) initially admitted to a tertiary hospital (on-site coronary angiography/angioplasty available) than in those (94 [32%] of 306) admitted to a community hospital (transfer to tertiary hospital for coronary angiography/angioplasty) (p less than 0.001). This different approach resulted in a greater use of coronary angioplasty (203 [18%] of 1,155 versus 32 [11%] of 306, p less than 0.01), coronary artery bypass surgery (133 [12%] of 1,155 versus 23 [8%] of 306, p less than 0.05) and blood transfusions (139 [12%] of 1,155 versus 17 [5.5%] of 306, p less than 0.001) in patients admitted to a tertiary than to a community hospital. However, there were no significant differences between the two groups in mortality, recurrent myocardial infarction or left ventricular function. These results demonstrate that a conservative strategy after treatment of acute myocardial infarction with rt-PA is applicable in the community hospital setting.

Angioplasty, Balloon, Coronary↗
PubMed1990

Impaired prostaglandin E1/I2 receptor activity of human blood platelets in acute ischemic heart disease.

The platelets from 74 patients with acute myocardial infarction or with unstable angina showed decreased prostaglandin E1/I2 receptor activity when compared with that of 56 normal volunteers by using [3H]prostaglandin E1 as a probe. In normals, Scatchard analyses showed the presence of one high-affinity-low-capacity (Kd1 = 9.0 +/- 1.2 nM [mean +/- SD]; n1 = 120 +/- 30 sites/cell) and one low-affinity-high-capacity (Kd2 = 1.1 +/- 0.5 microM; n2 = 1,460 +/- 250 sites/cell) prostaglandin E1/I2 receptor population in platelets. In contrast (p less than 0.01), platelets from patients showed decreased ligand binding (n1 = 40 +/- 20 sites/cell; n2 = 800 +/- 210 sites/cell) with little change in the affinity of the receptors (Kd1 = 7.50 +/- 1.6 nM; Kd2 = 0.68 +/- 0.24 microM). On the other hand, the platelets from the patients with dilated cardiomyopathy (n = 7) who were hospitalized for acute chest pain but had normal coronary arteries did not show any impairment of the receptor activity. The plasma prostacyclin level of the patients with acute ischemic heart disease was similar to that of normal volunteers; this finding indicated that the defective receptor function was not related to the prostaglandin receptors occupancy in vivo. The impaired receptor activity was temporary in nature. The follow-up studies showed that the prostaglandin receptor activity of the patients' platelets improved to "normal" levels within 2-8 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1989

Thrombolytic therapy in acute myocardial infarction: Part II--rt-PA.

Thrombolysis with pharmacologic agents is a valuable modality for treatment of acute myocardial infarction. The results of several clinical studies indicate that early recanalization can be elicited with intravenous agents and that it is associated with substantial reductions of infarct size, improvement of ventricular function, and reduction in mortality. The recently introduced fibrin-selective agent, rt-PA, appears to represent a significant pharmacologic advance. Its use intravenously elicits high recanalization rates without marked derangements of the coagulation system, reflecting its relative fibrin selectivity. The efficacy of thrombolysis with any drug given by any route, unfortunately, is not 100 per cent. Bleeding remains an important risk. The optimal approach to management of residual stenosis after thrombolysis has not yet been delineated. Currently available information appears to justify the following conclusions: 1. Transmural myocardial infarction usually is caused by an acute obstructing coronary thrombus superimposed on a chronic atherosclerotic lesion. Myocardial necrosis following interruption of blood flow generally is complete within several hours. 2. The thrombus can be lysed and blood flow can be restored with intravenous agents that activate plasminogen. Intravenous rt-PA, a relatively fibrin-specific agent, elicits recanalization in 70 to 75 per cent of infarct-related arteries. 3. Recombinant t-PA evokes only modest depletion of fibrinogen (16 to 36 per cent reduction from baseline). 4. Early reperfusion preserves myocardium and ventricular function and reduces mortality. 5. The extent of benefit after pharmacologic reperfusion is correlated strongly with the brevity of myocardial ischemia prior to initiation of therapy. The greatest benefit is realized in patients treated within the first few hours of onset of acute myocardial infarction. 6. The incidence and optimal means of prevention of reocclusion and reinfarction following successful pharmacologic reperfusion are not yet entirely clear. Mechanical recanalization with PTCA in conjunction with thrombolysis is promising, but its routine immediate use on an emergency basis does not appear to be beneficial. Vigorous educational efforts are needed to heighten the awareness of prospective patients and all members of the health care team to the value of prompt diagnosis of incipient or evolving infarction so that prompt implementation of thrombolysis in appropriate candidates can be facilitated.

Heart↗
PubMed1988

Specificity of oxygen radical scavengers and assessment of free radical scavenger efficiency using luminol enhanced chemiluminescence.

The selective scavenging capacities of 19 important oxygen radical scavengers were determined by adding them individually to each of the four oxy radical standards, (superoxide, hydroxy, alkoxy and hydroperoxy, and singlet O2), calculating the percent chemiluminescence inhibited, and extrapolating O2 equivalents neutralized from baseline. The sensitivity (0.01 nm/ml) and selectivity of this method not only allows identification of individual oxygen free radical species but also quantitates the efficiency of free radical scavengers.

Benzofurans↗
PubMed1988

Thrombolytic therapy in acute myocardial infarction: Part I.

Thrombolytic therapy with pharmacologic agents is an exciting approach to the treatment of myocardial infarction. The results of several clinical studies indicate that perfusion can be restored with intravenous therapy and may be associated with a reduction in infarct size and improved left ventricular function. In a trial involving more than 11,000 patients, thrombolytic therapy reduced acute and long term mortality. Pharmacologic thrombolysis, however, is not without problems. When administered intravenously, the agents currently available, streptokinase and urokinase, are associated with a relatively low recanalization rate as well as a risk of adverse effects, most commonly a systemic lytic state and risk of bleeding complications. Although intracoronary administration is associated with a higher rate of recanalization, the need for cardiac catheterization limits its applicability and results in a delay in the initiation of thrombolytic therapy (which diminishes salvage of myocardium). The trials assessing the existing agents have shown that time is a critical variable in the success of thrombolytic therapy. This had led investigators to focus more attention on intravenous agents that can be administered rapidly. The newer agents now under investigation, acylated streptokinase and single-chain urokinase, may represent improvements of currently available products and may offer potentially increased benefits. A fibrinogen-sparing agent, such as t-PA, in addition to being highly effective, may offer advantages through minimizing the systemic lytic effect. Additional randomized, controlled clinical trials currently are underway to determine the effect on mortality of this "fibrinolytic" therapy as part of a total treatment regimen. The current status of our knowledge concerning thrombolytic therapy in acute myocardial infarction can be summarized as follows: 1. Transmural (that is, Q wave) myocardial infarction usually is caused by an obstructing coronary thrombus. 2. The thrombus can be lysed with intravenous therapy in the majority of cases, particularly with newer, well-tolerated fibrin-specific agents. 3. There is considerable evidence suggesting that reperfusion reduces the acute morbidity and mortality when therapy is administered successfully within the initial 3 to 4 hours (and possibly up to 6 hours) after onset of symptoms. 4. Data on long term prognosis after thrombolysis are very encouraging, although limited. 5. Conventional agents lead to significant fibrinogen depletion and therefore an increased risk of bleeding; the new fibrin-selected agents cause less fibrinogen degradation and may reduce the risk of hemorrhagic complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiomyopathies↗
PubMed1988

Thrombolysis in myocardial infarction (TIMI): update 1987.

The "Thrombolysis in Myocardial Infarction" (TIMI) Trial, sponsored by the National Heart, Lung and Blood Institute, has evaluated the efficacy of coronary recanalization in acute myocardial infarction in different phases. TIMI Phase I compared the efficacy of recombinant tissue-type plasminogen activator (rt-PA) with that of streptokinase (SK) in a randomized double blind trial, using 80 mg rt-PA or 1.5 million units SK within 7 hours of clinical onset of infarction. rt-PA recanalized infarct related arteries in 62% compared to 31% with streptokinase. Bleeding complications were similar in both treatment groups and mainly related to vascular puncture sites during heart catheterization. The pharmacological dose of rt-PA, applied, caused a moderate effect on the proteins of the fibrinolytic system, but by far less than streptokinase. TIMI Phase 1.5 compared two preparations of rt-PA, the early formulation in liquid excipient ("old" rt-PA) and the new lyophilized form ("new" rt-PA). With equal dosage regimens of 80 mg, coronary recanalization rates at 90 minutes of infusion were 62% (old rt-PA) and 45% (new rt-PA). The lower recanalization potency of the new rt-PA is related to its shorter plasma half life. Three dosage regimens were evaluated with the new rt-PA, using 80 mg, 100 mg and 150 mg. Coronary recanalization rates were 45%, 71% and 76%, respectively. The dosage of 150 mg achieved the highest recanalization rates at 30 minutes of infusion, 42%. A linear trend test indicated a significant relation (p less than 0.001) between the dose of rt-PA and effects of the proteins of the fibrinolytic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗