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Biomedical subjects

R C Becker

Publications and source records attributed to R C Becker.

At least 91 records · Page 5Linked to original sources
PubMed1992

Thrombin antagonists and antiplatelet agents.

The clinical benefits of thrombolytic therapy for the treatment of myocardial infarction are recognized widely. However, 2 major limiting factors have become evident: (1) 20-25% of coronary arterial thrombi are resistant to lysis; and (2) coronary reocclusion occurs in 10-15% of patients. There is increasing evidence that both phenomena are caused by heightened procoagulant activity localized primarily at the site of atheromatous plaque rupture. Thrombin, the pivotal enzyme in all coagulation processes, is activated, stimulating fibrin formation and platelet aggregation. Platelet activation, by thrombin- and nonthrombin-mediated mechanisms, occurs as well, further increasing thrombotic tendency. Thus, a potent and well-localized procoagulant state may be continuously amplified, increasing both during and frequently after thrombolytic therapy. Current treatment strategies are designed to enhance fibrinolytic and anticoagulant activity, while neutralizing the expression of procoagulant factors. Thrombin antagonism and platelet inhibition, primarily with heparin and aspirin, respectively, form the mainstay of conjunctive therapy. Their benefits have been recognized, decreasing thromboembolic events and patient mortality. However, intrinsic limitations suggest that more potent and selective agents will be required to overcome effectively the problems of thrombolytic resistance and coronary reocclusion. In experimental models, specific thrombin antagonists and antiplatelet agents have shown superiority over heparin and aspirin. Further investigation to define the overall safety and efficacy profile of these newer agents will be required, however, prior to their widescale implementation in clinical practice.

Antithrombins↗
PubMed1992

Recurrent myocardial ischemia following thrombolytic therapy: guidelines for practicing clinicians.

The natural history of patients with acute myocardial infarction treated with thrombolytic therapy includes two distinct phases: the initial or acute phase is characterized pathologically by atheromatous plaque rupture and thrombotic coronary arterial occlusion, and clinically by the abrupt onset of symptoms. Prompt restoration of coronary blood flow and myocardial reperfusion during this phase, achieved in a majority of patients given thrombolytic therapy, limits myocardial necrosis, preserves ventricular function, and lowers mortality. Although the thrombus can be pharmacologically removed, an unstable anatomic substrate persists. Therefore following thrombolytic therapy, a subacute phase occurs, during which patients are at risk for recurrent ischemic events. More than a theoretical concept, experience has shown that recurrent ischemia and reinfarction develop in 20% to 30% and 5% of patients, respectively. Morbidity and mortality are elevated considerably in these patients, dictating an aggressive diagnostic and treatment approach.

Angioplasty, Balloon, Coronary↗
PubMed1992

Seminars in thrombosis, thrombolysis, and vascular biology. 6. Procoagulant states.

Under normal physiologic conditions, blood flows freely within the coronary arteries and peripheral vasculature, providing oxygen and essential nutriments to vital organs and metabolically active tissues. The natural thromboresistant properties of the vascular endothelium and circulating blood components provide the ideal environment for this fundamental, life-sustaining process. While hemostasis is a vital defense mechanism, preventing blood loss and ensuring rapid vessel repair, nonphysiologic thrombosis or 'hemostasis in the wrong place' may impair blood flow enough to cause debilitating or life-threatening tissue damage. Procoagulant (prothrombotic) states promote nonphysiologic thrombosis and reflect one or more significant abnormalities in either the vessel wall, circulating blood, or plasma coagulation components themselves. Although a heightened thrombotic tendency may be the end result of a focal or systemic pathologic process, in either case, thromboembolic events involving the cardiovascular system may ensue.

Blood Coagulation Factors↗
PubMed1992

Relationship between serum total cholesterol, infarct size, and early clinical outcome following acute myocardial infarction.

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk factors, including hypercholesterolemia, systemic hypertension, and cigarette smoking. Indeed, primary and secondary intervention trials have provided evidence for cholesterol lowering as an efficient method of CHD risk reduction. To test the hypothesis that serum total cholesterol influences the clinical outcome following acute myocardial infarction, infarct size, left ventricular ejection fraction, infarct-related vessel patency, and in-hospital cardiac events were determined in 106 consecutive patients given thrombolytic therapy within 5 h of symptom onset. Cumulative 48-hour creatine kinase (CK) release, peak CK, and calculated infarct size did not differ significantly between patients with an admitting serum total cholesterol level less than 200 mg/dl (group 1) and those with a cholesterol level greater than 250 mg/dl (group 2). Total cholesterol did not correlate with either cumulative CK release, peak CK, infarct size, vessel patency, or left ventricular ejection fraction. The vessel patency correlated inversely with cumulative CK release (r = -0.27; p = 0.03) and directly with left ventricular ejection fraction (r = 0.24; p = 0.03). The incidence of in-hospital cardiac events including recurrent infarction, congestive heart failure, and death was 6.9, 13.9, and 2.6%, respectively, and did not differ significantly between patient groups. Thus, although serum total cholesterol has been shown to influence CHD incidence, morbidity, and overall mortality, the findings of our study suggest that it does not impact directly on infarct size, left ventricular function, or in-hospital clinical outcome among patients sustaining acute myocardial infarction.

Cholesterol↗
PubMed1991

Adjunctive use of beta-adrenergic blockers, calcium antagonists and other therapies in coronary thrombolysis.

The availability of thrombolytic agents for use in the treatment of acute myocardial infarction is an important step in the management of a common, often debilitating, and potentially lethal disorder. However, despite the proven benefits of coronary thrombolysis, the importance of adjunctive treatment modalities is being increasingly recognized. Beta-adrenergic blockers, calcium antagonists, nitrates, magnesium, and angiotensin-converting enzyme inhibitors each exert favorable cardiovascular properties that may offer additional benefits. Clinical trials combining thrombolytic and adjunctive pharmacologic agents offer hope for further advances in the treatment of acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1991

Recombinant tissue-type plasminogen activator: current concepts and guidelines for clinical use in acute myocardial infarction. Part II.

The extraordinarily high prevalence of coronary heart disease, coupled with the alarming incidence of MI in Western society, has encouraged the investigation and development of pharmacologic agents that can be employed widely, quickly, effectively, and safely. Recombinant t-PA has played a vital role in the treatment of MI, restoring coronary arterial patency, limiting infarct size, preserving ventricular function, and improving patient survival. It has been shown to be safe when given to carefully selected patients and, although indications for clinical use have been relatively restricted, they appear to be expanding considerably. Future investigations must continue to focus on patient selection to allow treatment for all patients who would derive benefit and to establish dosing regimens and adjuvant therapies that will maximize coronary reperfusion while concomitantly limiting reocclusion and hemorrhagic complications.

Blood Platelets↗
PubMed1991

Seminars in thrombosis, thrombolysis and vascular biology. 1. The vascular endothelium.

The vascular endothelium, once believed to act solely as a mechanical barrier is, in fact, the body's most active paracrine organ serving a vital role in vasomotion and thromboresistance. Vasoactive compounds such as prostacyclin and endothelium-derived relaxing factor maintain coronary blood flow in response to physiologic demands, while their antiplatelet effects act along with tissue plasminogen activator and heparin-like species to prevent local thrombus formation. Structural and functional endothelial abnormalities may predispose to vascular thrombosis or impair normal vasodilatory responses to increasing metabolic demands. Acquired endothelial dysfunction following coronary reperfusion, aortocoronary bypass grafting and balloon angioplasty plays a vital role in short- and long-term patient outcome. Future therapies in cardiovascular disease must consider strategies to preserve and facilitate the structural and functional integrity of the vascular endothelium.

Angioplasty, Balloon, Coronary↗
PubMed1991

Seminars in thrombosis, thrombolysis, and vascular biology. Part 2: Coagulation and thrombosis.

The hemostatic mechanism is a critical component of a normally functioning circulatory system, preventing life-threatening hemorrhage and assisting in the maintenance of vascular integrity. For longer than half a century, however, nonphysiological intravascular coagulation and thrombosis have been recognized as playing central roles in cardiovascular morbidity and mortality. In order to provide a conceptual framework for the use of antithrombotic therapy, the pathogenetic mechanisms underlying thrombotic events must be clearly understood. The purpose of this review is to define these mechanisms, and discuss the use of anticoagulants in both the prevention and treatment of cardiovascular diseases.

Anticoagulants↗
PubMed1991

Heparin pharmacokinetics and in vitro anticoagulant activity in patients receiving nonionic radiographic contrast media.

Nonionic radiographic contrast media are used frequently in diagnostic and interventional angiography. However, there is concern that they may possess thrombogenic properties, and some studies have suggested that patients receiving nonionic contrast media are difficult to systemically anticoagulate with intravenous heparin. To investigate the potential effects of nonionic contrast media on systemic anticoagulation during diagnostic cardiac catheterization, pharmacokinetics and in vitro anticoagulant activity following a 3,000 U intravenous heparin bolus were assessed in 12 patients assigned randomly to either an ionic or a nonionic contrast agent. Independent of contrast agent, all patients exhibited biphasic (nonlinear) heparin pharmacokinetics characterized by an initial rapid disappearance phase, followed by a second slower phase. Each patient achieved a therapeutic plasma heparin concentration (greater than or equal to 0.2 U/ml) within 10 min of receiving the bolus, and maintained this level throughout the procedure. Heparin anticoagulant activity, as estimated by a standard activated partial thromboplastin time (APTT) was not affected differently by nonionic as compared with ionic contrast media (p greater than 0.05). Each patient rapidly achieved a level of systemic anticoagulation commonly considered therapeutic (APTT greater than or equal to 1.5 times the control), and maintained this level throughout the procedure. In both groups, APTT correlated directly with plasma heparin concentration (r = 0.95; p less than 0.0001), and inversely with the total amount of contrast media used during the procedure (r = -0.25; p = 0.01). Plasma heparin concentration did not correlate with total contrast media (r = -0.16; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1991

Seminars in thrombosis, thrombolysis and vascular biology. 3. Platelet activity in cardiovascular disease.

Platelets contribute to normal hemostasis by adhering to subendothelial tissues after vascular damage has taken place and then recruiting additional platelets through the process of aggregation. Activation of the coagulation cascade ultimately results in fibrin deposition. In pathological conditions, thrombogenic surfaces act as a nidus for platelet adherence and thrombus formation. The ability of platelet-inhibiting agents to prevent or impair platelet-mediated thrombotic and thromboembolic events is of vital importance in the prevention and treatment of cardiovascular diseases, including myocardial infarction, unstable angina and stroke. They also serve as important adjuvants following percutaneous transluminal coronary angioplasty and saphenous vein bypass grafting. Future investigations will likely uncover additional indications.

Blood Platelets↗
PubMed1991

Seminars in thrombosis, thrombolysis and vascular biology. 4. Fibrinolysis.

In general terms, thrombotic disorders of the cardiovascular system are characterized by poorly regulated, nonphysiologic thrombus formation. Considered more specifically, however, pathologic thrombosis represents a critical imbalance, frequently at both the systemic and vascular levels, of coagulation, anticoagulation and fibrinolysis. Indeed, the balance is shifted toward coagulation, preventing normal physiologic blood flow. Anticoagulants have been a mainstay in the treatment of thrombotic disorders. However, emerging strategies have focused primarily on thrombus dissolution (fibrinolysis), which can be efficiently achieved with the administration of extrinsic plasminogen activators. Clearly, thrombolytic therapy is currently the most direct means of restoring blood flow, vital organ perfusion and hemostatic balance among patients with thrombotic disorders of the cardiovascular system.

Angina, Unstable↗
PubMed1991

Effect of serum total cholesterol on hemorrhagic complications following thrombolytic therapy for acute myocardial infarction.

Despite the well-known and widely publicized adverse effects of hypercholesterolemia on the cardiovascular system, cholesterol is a vital component of cellular membranes, maintaining vascular integrity and normal platelet activatability. To test the hypothesis that a low serum total cholesterol concentration increases bleeding risk following thrombolytic therapy, a comparison of in-hospital hemorrhagic events was made between 132 patients with myocardial infarction divided into three distinct groups. Group 1 patients (n = 44) had an admitting serum total cholesterol of less than 200 mg/dl, while group 2 (n = 57) and group 3 (n = 31) patients had cholesterol levels of 200-249 and greater than or equal to 250 mg/dl, respectively. There were no significant differences between groups in either minor hemorrhagic events (p = 0.85), major hemorrhagic events (p = 0.73) or transfusion requirements (p = 0.45). In addition, the primary sites of bleeding did not differ. Over the 2-year study period, a total of four intracerebral events were identified. As with minor and other major hemorrhagic events, an association with serum total cholesterol and intracerebral hemorrhage was not observed (p = 0.29). However, advanced age (greater than 65 years; p = 0.04) and a total dose of recombinant tissue-type plasminogen activator in excess of 1.5 mg/kg body weight (p less than 0.001) were identified by multivariate analysis as risk factors for intracerebral hemorrhage. Thus, although cholesterol is vital for maintaining vascular integrity and normal hemostasis, relatively low serum levels are not a risk factor for hemorrhagic complications following thrombolytic therapy.

Aged↗
PubMed1991

Seminars in thrombosis, thrombolysis, and vascular biology. Part 5: Cellular rheology and plasma viscosity.

The fundamental determinants of coronary blood flow include the vessel radius, pressure gradient, and the physical characteristics of the cellular components and fluid medium. Specifically, cellular rheology and plasma viscosity determine, to a significant degree, both macro- and microcirculatory blood flow, particularly when either is compromised by existing atherosclerotic narrowing or reperfusion injury. Among individuals with coronary heart disease, abnormalities in cellular rheology and plasma viscosity may be the best predictors of subsequent cardiac events. Therefore, efforts to limit morbidity and mortality may depend on a more in-depth understanding of these basic areas.

Blood Flow Velocity↗