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Biomedical subjects

R C Becker

Publications and source records attributed to R C Becker.

At least 73 records · Page 4Linked to original sources
PubMed1994

Beta-adrenergic blockade following thrombolytic therapy: is it helpful or harmful?

Beta-adrenergic blockade has been a mainstay in the treatment of patients with acute myocardial infarction for nearly two decades. Clearly, it has withstood the test of time. The emergence of thrombolytic therapy, however, has shifted the medical community's focus, raising questions as to the benefit of beta-adrenergic blockade. Although further investigation is warranted, the available evidence suggests that beta blockers can be given safely to selected patients following coronary thrombolysis, particularly in the absence of moderate to severe left ventricular dysfunction.

Adrenergic beta-Antagonists↗
PubMed1994

Bedside coagulation monitoring in heparin-treated patients with active thromboembolic disease: a coronary care unit experience.

Patients with active venous and arterial thromboembolic disorders are known to benefit from systemic anticoagulation with heparin. Clinical studies have shown, however, that therapeutic anticoagulation is rarely achieved rapidly and often is not maintained over time. Prolonged laboratory turnaround time of the activated partial thromboplastin time (aPTT) may contribute directly to these common problems. A total of 272 aPTT determinations were performed on 120 heparin-treated patients admitted to the coronary care unit. The time from sample collection to data availability was 126 +/- 84 minutes with standard laboratory aPTT testing. In contrast, a bedside coagulation device provided an aPTT within 3 minutes (p < 0.001). Subtherapeutic aPTT values (< 65 seconds) were documented in 21% of all patients; in each, the heparin dose was changed and a repeat aPTT was required. In a separate study of 33 heparinized patients randomized to either bedside or central laboratory aPTT testing (264 aPTT determinations), the time to achieve a therapeutic state of systemic anticoagulation was 8.2 hours and 18.1 hours, respectively (p < 0.005). The time from aPTT determination to a decision regarding heparin titration adjustments was 14.5 minutes and 3 hours with bedside and laboratory testing, respectively (p < 0.001). Thus bedside coagulation monitoring provides a convenient, rapid, and accurate assessment of systemic anticoagulation among heparin-treated patients with active thromboembolic disease in the coronary care unit. This technology warrants further clinical investigation.

Coronary Care Units↗
PubMed1994

Expanding the paradigm of the renin-angiotensin system and angiotensin-converting enzyme inhibitors.

The renin-angiotensin system acts systemically and locally to influence vascular tone, blood volume, myocardial contractility, thromboresistance, and tissue responses to injury. ACE inhibitors have assumed a vital role in the treatment of patients with ventricular dysfunction, including those who have sustained one or more myocardial infarctions. The greatest benefits appear over time and not unexpectedly are most pronounced in cases of moderate to severe reduction in left ventricular performance. Emerging evidence suggests that the paradigm for ACE inhibitor use will expand even further, opening new doors for patient care.

Angiotensin-Converting Enzyme Inhibitors↗
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

The clinical use of flow cytometry for assessing platelet activation in acute coronary syndromes. TIMI-III Thrombosis and Anticoagulation Group.

BACKGROUND: Unstable angina signals a sudden transition from stable to unstable atherosclerotic coronary artery disease. Although assessment of platelet activity has been shown to provide diagnostic and prognostic information, most available methods lack sufficient sensitivity or specificity for them to be useful in clinical practice. In recent years, fluorescently labeled antibodies and flow cytometry have permitted the detection of activation proteins on individual platelets. The purpose of the present study was to assess the ability of flow cytometry to detect platelet activation in patients with unstable angina and non-Q-wave myocardial infarction. METHODS: Platelet activation before treatment was determined from whole-blood samples in 19 patients participating in the Thrombolysis in Myocardial Ischemia (TIMI)-IIIB study and in nine healthy volunteers (total of 24 samples) using flow cytometry and a monoclonal antibody (clone 1E3) to the activation-dependent, surface-expressed protein P-Selectin. RESULTS: Among healthy volunteers, a small percentage of platelets were activated (2.0 +/- 2.5%). In contrast, 15 out of 19 (79%) patients with suspected myocardial ischemia at rest had 10.4 +/- 11.1% activated platelets (95% confidence interval 4.9-15.9%; P < 0.01). Seven patients (37%) were found to have more than 10% activated platelets. The degree of platelet activation did not differ significantly between patients with unstable angina and those with elevated creatine kinase levels (non-Q-wave myocardial infarction). CONCLUSION: Whole-blood flow cytometric techniques can minimize the artifactual platelet activation often seen with other techniques and therefore offer distinct advantages in the investigation of patients with thrombotic coronary syndromes. In TIMI-III, patients with unstable angina and non-Q-wave myocardial infarction had clear evidence of platelet activation. An ongoing study will examine the correlation between platelet activation assessed using flow cytometry and clinical events in a larger patient cohort.

Acute Disease↗
PubMed1993

Cardiogenic shock: elements of etiology, diagnosis, and therapy.

Cardiogenic shock usually is the result of marked depression in myocardial function. Rapid recognition and stabilization are essential if the patient is to survive. A variety of cardiovascular conditions can lead to cardiogenic shock; the most common of these is acute myocardial infarction. Once stabilization of the cardiogenic shock patient has been effected, hemodynamic monitoring and definitive therapy should be attempted if appropriate. Intra-aortic balloon counterpulsation is effective in stabilizing these patients temporarily. Definitive therapy may include surgical or catheterization interventions. Mortality, even under the best of circumstances, remains high.

Humans↗
PubMed1993

Thrombolytic agents and anticoagulants.

The medical and scientific communities, appreciating the pivotal role of thrombosis in the evolution and expression of atherosclerotic coronary artery disease, have embarked upon intense efforts to develop safe, effective, and affordable thrombolytic agents and anticoagulants. With an understanding that more is not always better, these new compounds, mutants, and derivatives will be designed specifically to impair, neutralize, or enhance several key components of well-characterized thrombotic and fibrinolytic processes. If efforts continue at the current pace, one or more "designer" thrombolytics and anticoagulants will be ready for Phase II or Phase III clinical trials in the near future.

Anticoagulants↗
PubMed1993

Hemodynamic, mechanical, and metabolic determinants of thrombolytic efficacy: a theoretic framework for assessing the limitations of thrombolysis in patients with cardiogenic shock.

Although thrombolytic therapy has been shown to limit infarct size, preserve left ventricular function, and improve survival in most subgroups of patients with acute MI, a benefit has not been demonstrated in patients with clinical left ventricular dysfunction or overt cardiogenic shock before treatment is initiated. The reason(s) for the lack of benefit derived from thrombolytic therapy in these settings is unclear. Left ventricular dysfunction and overt cardiogenic shock are the result of extensive myocardial necrosis, typically in excess of 30% of the left ventricle, which progresses over time. The available data suggest that thrombolytic efficacy is decreased because of either hemodynamic, mechanical, or metabolic factors. As a result coronary patency is rarely achieved in a timely fashion, and if patency is achieved it typically is not maintained. The ability of mechanical revascularization by means of balloon angioplasty to reduce mortality suggests that reperfusion is a key determinant of outcome even among patients with large infarctions and early signs of left ventricular dysfunction. Thrombolytic therapy, which is widely available and extensively tested, represents the standard of care for patients with acute MI. Its apparent lack of efficacy in patients with congestive heart failure and cardiogenic shock is poorly understood. Further investigation must therefore be undertaken.

Hemodynamics↗
PubMed1993

Hemorrhagic potential of combined diltiazem and recombinant tissue-type plasminogen activator administration.

In the Thrombolysis in Myocardial Infarction (TIMI) phase II study, use of calcium channel antagonists at study entry was associated with an increased risk of intracerebral hemorrhage. Whether the observed association was due solely to chance, underlying cerebrovascular disease, or an effect of calcium channel antagonists themselves was not determined. Accordingly, blood loss from standardized ear incisions was measured in six groups of anesthetized New Zealand white rabbits: (1) saline control, (2) intravenous diltiazem (20 micrograms/kg/min x 60 minutes), (3) intravenous recombinant tissue-type plasminogen activator (rTPA) (1.0 mg/kg over 60 minutes, 10% bolus), (4) diltiazem plus rTPA, (5) diltiazem daily for 3 consecutive days, and (6) diltiazem (3 days) plus rTPA given on day 3. The combination of rTPA plus diltiazem (3 days) resulted in significantly more blood loss than rTPA alone, diltiazem (60-minute infusion), or rTPA plus diltiazem (60-minute infusion) (p = 0.003). Similarly, diltiazem (3 days) resulted in more blood loss than either agent alone or rTPA plus diltiazem (60-minute infusion) (p < 0.05). Thus, in this animal model, prolonged exposure to diltiazem with or without rTPA was associated with increased bleeding. The potential for chronic use of oral calcium channel antagonist to increase hemorrhagic risk after rTPA administration requires further investigation.

Animals↗
PubMed1993

Reocclusion following successful thrombolysis. Emerging concepts.

Thrombolytic therapy, through the restoration of coronary arterial blood flow and myocardial perfusion significantly improves outcome among patients with acute myocardial infarction. Despite its widely appreciated benefits, however, thrombolysis removes only a small portion of existing thrombus at the site of atheromatous plaque rupture. Further, thrombogenic substrate is frequently exposed and may even be generated to the extent that rethrombosis occurs, causing recurrent ischemia, reinfarction, and coronary reocclusion. The mechanisms underlying this important event are discussed.

Angioscopy↗
PubMed1993

The challenge of maintaining coronary arterial patency with intravenous heparin following tissue plasminogen activator administration.

It is widely accepted that coronary arterial patency, achieved early after symptom onset and maintained over time, is an absolute prerequisite for patient benefit following thrombolytic therapy. Conjunctive pharmacological agents such as heparin appear to play an important role in maintaining vessel patency, particularly following tissue plasminogen activator (t-PA) administration. Unfortunately, dosing strategies and monitoring have not kept pace with the rest of the field. Further investigation is encouraged.

Administration, Oral↗
PubMed1993

Late thrombolytic therapy: mechanism of benefit and potential risk among patients treated beyond 6 hours.

BACKGROUND: Thrombolytic therapy is the treatment of choice for many patients with myocardial infarction, particularly those presenting to the hospital within 6 hours from symptom onset. Although prompt treatment promises to provide the greatest overall benefit, delayed thrombolysis (possibly beyond a time when myocardial salvage is achieved) may also have a role in current clinical practice. METHODS: A review of the English-language literature was conducted by MEDLINE search. Pertinent references were found as far back as 1912. RESULTS: Results of several nonrandomized clinical studies and one recently completed randomized study (the Late Assessment of Thrombolytic therapy Efficacy [LATE]) suggest that thrombolytic therapy may be beneficial up to 12 hours from the onset of symptoms. The mechanisms of benefit are poorly defined, but they may include myocardial salvage, reduced early infarct zone expansion, improved healing, and decreased ventricular irritability. These mechanisms are not necessarily exclusive of one another. An increased risk of myocardial rupture and thromboembolism may be incurred, limiting the usefulness of treatment with further delay. CONCLUSIONS: Delayed thrombolysis (up to and possibly beyond 12 hours from symptom onset in certain patient subgroups) reduces patient mortality. Despite increasing support, however, many patients, even those seeking medical treatment within 6 hours, are not being given thrombolytic therapy. Further investigation into this area must be undertaken. The Benefits of Late Thrombolysis (BOLT) study should provide much needed information.

Clinical Trials as Topic↗
PubMed1993

Antiplatelet therapy in coronary heart disease. Emerging strategies for the treatment and prevention of acute myocardial infarction.

Platelets, long recognized for their role in physiological (protective) hemostasis, have been shown conclusively to play an intricate role in both coronary arterial atherogenesis and acute thrombosis. Accordingly, antiplatelet agents have emerged as a prominent feature in treatment strategies designed to prevent and directly confront the progression and thrombotic complications of coronary heart disease in humans. Antiplatelet therapy, used alone or in combination with thrombin antagonists and thrombolytics must be explored with continued enthusiasm to assure growth of this treatment modality.

Animals↗
PubMed1993

Mechanisms and management of cardiogenic shock.

Cardiogenic shock remains the most dreaded complication of acute myocardial infarction. Mortality rates remain high despite modern interventional therapy. Patients with a variety of other cardiovascular entities may also develop cardiogenic shock. Management consists of rapid stabilization of systemic arterial blood pressure, expeditious diagnostic evaluation, and definitive therapy when possible. New therapeutic modalities will be needed if patients with cardiogenic shock are to survive.

Critical Care↗