fibrin and Myocardial-Ischemia

Several third-generation thrombolytic agents have been developed. They are either conjugates of plasminogen activators with monoclonal antibodies against fibrin, platelets, or thrombomodulin; mutants, variants, and hybrids of alteplase and prourokinase (amediplase); or new molecules of animal (vampire bat) or bacterial (Staphylococcus aureus) origin. These variations may lengthen the drug's half-life, increase resistance to plasma protease inhibitors, or cause more selective binding to fibrin. Compared with the second-generation agent (alteplase), third-generation thrombolytic agents such as monteplase, tenecteplase, reteplase, lanoteplase, pamiteplase, and staphylokinase result in a greater angiographic patency rate in patients with acute myocardial infarction, although, thus far, mortality rates have been similar for those few drugs that have been studied in large-scale trials. Bleeding risk, however, may be greater.

Topics: Clinical Trials as Topic; Drug Evaluation; Fibrin; Fibrinolytic Agents; Half-Life; Humans; Myocardial Ischemia; Plasminogen Activators; Thrombolytic Therapy; Thrombomodulin

Topics: Adult; Arteries; Arteriosclerosis; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Myocardial Ischemia; Reference Values; Thrombosis

It was only quite recently that the thrombotic component in myocardial infarction and sudden coronary death was generally acknowledged. When attention was eventually paid to it, interest initially centered primarily on platelet function. There is, of course, no doubt about the central role of platelet adhesion and aggregation in thrombogenesis, but still no generally accepted measure of platelet function has been shown to be associated with the later onset of ischemic heart disease (IHD). Epidemiologically, the assessment of coagulability has been more rewarding. Several prospective studies have now shown a strong relationship between the plasma fibrinogen level and the incidence of IHD and stroke. Epidemiologic and laboratory studies have also implicated factor VII and extrinsic pathway activity in the onset of IHD. Other components of the hemostatic system that are probably involved include factor VIII activity and the fibrinolytic system. It is increasingly clear that lipoproteins exert a major influence on coagulability as well as their better known role in atherogenesis. Any further polarization of hypotheses for IHD as being purely atherogenic or purely thrombogenic is therefore counterproductive. At the same time, antithrombotic measures for primary prevention need to be evaluated as thoroughly as lipid-lowering regimens. If thrombosis is seen as the final arterial event in virtually all major episodes of IHD, the indications for antithrombotic agents in primary prevention may be wider than those for lipid-lowering regimens. It is therefore necessary to establish as quickly as possible not only the preventive effectiveness of antithrombotic measures, including low-dose aspirin and low-intensity oral anticoagulation, but also the relative effectiveness and safety of antithrombotic and lipid-modifying regimens.

Topics: Blood Platelets; Fibrin; Hemostasis; Humans; Myocardial Infarction; Myocardial Ischemia; Thrombosis

Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding.. In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding.. A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.

Topics: Aged; Anticoagulants; Azetidines; Benzylamines; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Partial Thromboplastin Time; Peptide Fragments; Protein Precursors; Prothrombin; Risk Factors; Thrombin

Diagnosis of acute coronary syndromes (ACS) is a major challenge for emergency physicians. Because soluble fibrin (sF) has been suggested as a potential early marker of impending myocardial ischemia, we were interested whether a sF bedside test could help in early identification of patients with ACS in the emergency department.. We evaluated plasma coagulation markers, including a newly developed sF bedside test, prothrombin fragment (F(1+2)), sF, and D-dimer, in a cross-sectional trial with 184 patients suggestive of ACS.. Whereas 76% (13 of 17) of patients with unstable angina pectoris (UAP) had a positive sF bedside test, only 10 of 33 patients (30%) with non-ST-segment-elevation myocardial infarction and 10 of 44 patients (23%) with ST-elevation myocardial infarction tested positive. Three percent of controls (1 of 33) and 11% of patients (6 of 57) with preexisting stable angina had a positive sF bedside test (P <0.001 for noncardiac chest pain vs ACS), yielding an overall specificity of 92% and a sensitivity of 35%. The sensitivity of the established coagulation markers was significantly less to detect ACS (11% for F(1+2), 20% for thrombus precursor protein, and 18% for D-dimer; P <0.02 vs sF bedside test). The sF bedside test presented the earliest objective indicator of impending myocardial damage in the majority (10 of 13) of ACS patients with a normal or nondiagnostic electrocardiogram (ECG).. A sF bedside test offers a specific tool for early identification of patients with ACS in an emergency department setting, although its sensitivity seems sufficient only for the early identification of patients with UAP. A sF bedside test could be useful, particularly in UAP patients with a nondiagnostic ECG.

Topics: Acute Disease; Angina, Unstable; Biomarkers; Blood Coagulation Tests; Emergency Medical Services; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Point-of-Care Systems; Sensitivity and Specificity

Poor cell homing limits the efficacy of cardiac cellular therapy. The homing peptide, cysteine-arginine-glutamic acid-lysine-alanine (CREKA), targets fibrin effectively which is involved in the repair process of tissue injury. Here, we assessed if CREKA-modified stem cells had enhanced fibrin-mediated homing ability resulting in better functional recovery and structural preservation in a rat myocardial injury model. CREKA-modified mesenchymal stem cells (CREKA-MSCs) were obtained via membrane fusion with CREKA-modified liposomes. The fibrin targeting ability of CREKA-MSCs was examined both in vitro and in vivo. Under both static and flow conditions in vitro, CREKA significantly enhanced MSCs binding ability to fibrin clots (2.6- and 2.3-fold, respectively). CREKA-MSCs showed 6.5-fold higher accumulation than unmodified MSCs in injured rat myocardium one day after administration, resulting in better structural preservation and functional recovery. Fibrin is, therefore, a novel target for enhancing homing of transplanted cells to injured myocardium, and the delivery system of fibrin-targeting is on behalf of a universalizable platform technology for regenerative medicine. Stem Cells 2019;37:663-676.

Topics: Animals; Disease Models, Animal; Drug Delivery Systems; Fibrin; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Ischemia; Myocardium; Nanoparticles; Oligopeptides; Rats; Reperfusion Injury

Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury.

Topics: Animals; Base Sequence; Cells, Cultured; Disease Models, Animal; DNA Primers; Fibrin; Human Umbilical Vein Endothelial Cells; Humans; Insulin-Like Growth Factor I; Myocardial Ischemia; Stem Cell Transplantation; Swine

Fibrin is an extracellular matrix protein that is responsible for maintaining the structural integrity of blood clots. Much research has been done on fibrin in the past years to include the investigation of synthesis, structure-function, and lysis of clots. However, there is still much unknown about the morphological and structural features of clots that ensue from patients with disease. In this research study, experimental techniques are presented that allow for the examination of morphological differences of abnormal clot structures due to diseased states such as diabetes and sickle cell anemia. Our study focuses on the preparation and evaluation of fibrin clots in order to assess morphological differences using various experimental assays and confocal microscopy. In addition, a method is also described that allows for continuous, real-time calculation of lysis rates in fibrin clots. The techniques described herein are important for researchers and clinicians seeking to elucidate comorbid thrombotic pathologies such as myocardial infarctions, ischemic heart disease, and strokes in patients with diabetes or sickle cell disease.

Topics: Anemia, Sickle Cell; Blood Chemical Analysis; Factor XIIIa; Fibrin; Fibrinogen; Fibrinolysis; Humans; Microscopy, Confocal; Myocardial Infarction; Myocardial Ischemia; Stroke; Thrombin; Thrombosis

To evaluate the biocompatibility and biodegradability of various hydrogels and choose suitable hydrogels for the coronary arteries angiogenesis in ischemic myocardium, we synthesized six kinds of hyaluronan hydrogels, fibrin hydrogel, poly(vinyl alcohol)-chitosan hydrogel, and obtained elastin hydrogels. We examined their degradation rates and cytotoxicity in vitro. Then, hydrogels were implanted into rat adductor muscles for 1, 2, or 4 weeks. Hydrogels and surrounding tissues were resected, followed by hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemical staining for measurements of degradation, immune response, and angiogenesis. 2-Iminothiolane grafted hyaluronan hydrogel and periodate oxidated hyaluronan hydrogel presented rapid degradation rates, low quantity of inflammation-mediating cells (12 +/- 3 and 12 +/- 4 per 2.5 x 10(-3) mm(2), respectively, at week 2), thin fibrous capsules (scores were 3.8 +/- 0.1 and 4.0 +/- 0.3 per 0.33 mm(2), respectively, at week 2) with dense blood vessels in the areas surrounding the implanted hydrogels. 2-Iminothiolane grafted hyaluronan and periodate oxidated hyaluronan hydrogels with appropriate degradation rates and low immune responses were suitable for coronary arteries angiogenesis in ischemic myocardium.

Topics: Animals; Biocompatible Materials; Cells, Cultured; Chitosan; Coronary Vessels; Drug Carriers; Elastin; Fibrin; Gene Transfer Techniques; Hyaluronic Acid; Hydrogels; Inflammation; Male; Materials Testing; Muscle, Skeletal; Muscle, Smooth, Vascular; Myocardial Ischemia; Neovascularization, Physiologic; Pilot Projects; Polymers; Polyvinyls; Rats; Rats, Sprague-Dawley

We sought to test the prognostic performance of thrombus precursor protein (TpP) in patients presenting with an acute coronary syndrome (ACS).. Because thrombus formation is a critical step in the development of ACS, a measurement of activated coagulation could yield important information. Thrombus precursor protein is a biomarker that is used to measure soluble fibrin polymers, which are the penultimate products in fibrin formation.. We measured the levels of TpP in 284 healthy volunteers and in 2,349 patients with ACS.. Median TpP concentrations were 3.6 mug/ml (interquartile range 2.6 to 5.5) in the volunteers and 8.9 mug/ml (interquartile range 4.9 to 15.9) in the ACS patients (p < 0.001). Patients with ACS who had elevated TpP were older, more likely to be women, and more likely to have diabetes and pre-existing CAD (p < 0.02 for each). Thrombus precursor protein levels greater than the median were associated with a significantly increased risk for the composite of death, myocardial infarction (MI), or recurrent ischemia leading to rehospitalization or urgent revascularization through 10 months (hazard ratio [HR] 1.45, p < 0.001), as well as death or MI (HR 1.42, p = 0.02). We found that TpP correlated only weakly with cardiac troponin I, B-type natriuretic peptide, and high-sensitivity C-reactive protein (|r| <0.15 for each). After adjusting for clinical characteristics, cardiac troponin I, high-sensitivity C-reactive protein, and B-type natriuretic peptide, we found that patients with TpP levels greater than the median remained at significantly increased risk for the composite outcome (adjusted HR 1.51, p = 0.001) and death or MI (adjusted HR 1.58, p = 0.02).. In patients with ACS, increased levels of TpP are associated with an increased risk of death or ischemic complications. The incorporation of a marker of activated coagulation, such as TpP, with established cardiovascular risk factors may offer valuable complementary insight into risk assessment in ACS.

Topics: Acute Coronary Syndrome; Adult; Biomarkers; Blood Coagulation; C-Reactive Protein; Case-Control Studies; Coronary Thrombosis; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Ischemia; Odds Ratio; Prognosis; Risk Assessment; Treatment Outcome; Troponin I

Topics: Acute Coronary Syndrome; Biomarkers; Blood Coagulation; Fibrin; Humans; Myocardial Ischemia; Prognosis; Risk Assessment

Cardiopulmonary bypass and coronary artery bypass grafting (CABG) result in significant thrombin generation and activation of fibrinolysis. Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in myocardial damage after CABG is unknown.. We measured thrombin generation and fibrin turnover during reperfusion after CABG to evaluate their associations with postoperative hemodynamic changes and myocardial damage.. One hundred patients undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at seven time points thereafter. Mass of the Mb fraction of creatine kinase (Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day.. Reperfusion induced an escalation of thrombin generation and fibrin turnover despite full heparinization. F(1+2) during early reperfusion associated with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r = 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher F(1+2) during reperfusion than others (P < 0.002). Logistic regression models identified F(1+2) during reperfusion to independently associate with postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals 1.04-15.7).. Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.

Topics: Adult; Aged; Aged, 80 and over; Coronary Artery Bypass; Female; Fibrin; Heparin; Humans; Male; Middle Aged; Myocardial Ischemia; Postoperative Complications; Prospective Studies; Reperfusion Injury; Thrombin

Activation of coagulation and fibrinolysis is common among patients undergoing cardiopulmonary bypass (CPB) surgery. Little is known, however, about the impact of myocardial ischemia and reperfusion on coagulation activation and fibrinolysis in this clinical setting.. We determined the levels of coagulation activation and fibrinolysis markers (CAFM) in 19 patients with severe coronary heart disease (CHD) during CPB surgery. FXIIa, tissue factor (TF), FVIIa, tissue plasminogen activator/plasminogen activator inhibitor-1 complexes (tPA/PAI-1), prothrombin fragments 1+2 (F1+2), D-dimers (DD) and plasmin-plasmin inhibitor complexes (PPI) were measured at baseline, prior to and after cardioplegic myocardial ischemia. Simultaneous blood samples were drawn from the aorta and the coronary sinus to evaluate arteriovenous CAFM plasma level gradients.. Myocardial ischemia induced significant increases in gradients of FXIIa and F1+2 levels across the coronary circulation without influencing systemic levels of these markers significantly. Systemic levels of FXIIa, tPA/PAI-1, F1+2, DD and PPI increased significantly during CPB operation. There was a significant linear correlation between FXIIa, FVIIa, F1+2, DD and PPI.. Myocardial ischemia induces contact activation and thrombin generation rather than release of tPA and might thus contribute to postoperative thromboembolic complications. Surgery itself and CPB cause activation of coagulation and fibrinolysis as already described. A significant association between FXIIa, FVIIa, F1+2, DD and PPI suggests a relationship between contact activation, thrombin generation, fibrin formation and fibrinolysis.

Topics: Aged; Arteries; Biomarkers; Blood Coagulation Factors; Cardiopulmonary Bypass; Coronary Vessels; Female; Fibrin; Fibrinolysis; Hemostasis; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Reperfusion; Thrombin

Lp(a), a major cardiovascular risk factor, contains a specific apolipoprotein, apo(a), which by virtue of structural homology with plasminogen inhibits the formation of plasmin, the fibrinolytic enzyme. A number of clinical reports support the role of Lp(a) as a cardiovascular or cerebral risk factor, and experimental data suggest that it may contribute to atherothrombosis by inhibiting fibrinolysis.. A well-characterized model of a fibrin surface and an apo(a)-specific monoclonal antibody were used to develop a functional approach to detect pathogenic Lp(a). The assay is based on the competitive binding of Lp(a) and plasminogen for fibrin, and quantifies fibrin-bound Lp(a). High Lp(a) binding to fibrin is correlated with decreased plasmin formation. In a transversal case-control study we studied 248 individuals: 105 had a history of ischaemic cardiopathy (IC), 52 had cerebro-vascular disease (CVD) of thrombotic origin, and 91 were controls.. The remarkably high apo(a) fibrin-binding in CVD (0.268 +/- 0.15 nmol L-1) compared with IC (0.155 +/- 0.12 nmol L-1) suggests the existence of peculiar and poorly understood differences in pro- or anti-thrombotic mechanisms in either cerebral and/or coronary arteries.. Our results demonstrated that Lp(a) fibrin-binding and small Apo(a) isoforms are associated with athero-thrombotic disease.

Topics: Adult; Apolipoproteins A; Binding, Competitive; Biomarkers; Case-Control Studies; Cerebrovascular Disorders; Female; Fibrin; Fibrinolysin; Humans; Lipoprotein(a); Male; Middle Aged; Myocardial Ischemia; Plasminogen; Protein Binding; Protein Isoforms

We have shown that microvascular changes that promote fibrin deposition in human cardiac allografts adversely affect clinical outcome. However, some allografts exhibit phenotypic changes in capillaries following the deposition of fibrin, which subsequently provide a significant survival advantage. The mechanism(s) involved in these capillary changes is(are) unknown. Similarly, although we have shown a significant temporal relationship between microvascular fibrin deposition and vascular endothelial growth factor (VEGF) immunoreactivity in cardiac allografts, the cellular source and relative changes in VEGF gene expression under these conditions are not known. Using immunocytochemical techniques, biopsies devoid of fibrin deposition lacked detectable VEGF immunoreactivity, whereas biopsies with fibrin deposition showed VEGF immunoreactivity in cardiocytes, interstitium, and some microvessels. By in situ hybridization, biopsies without microvascular fibrin deposition showed faint VEGF hybridization signals confined primarily to cardiocytes. In biopsies with fibrin deposition, strong VEGF hybridization signals were detected in cardiocytes, arteriolar smooth muscle cells were occasionally labeled, and endothelial cells were rarely labeled. By quantitative RT-PCR, biopsies with fibrin deposition (n=5) relatively expressed approximately three-fold more VEGF mRNA than biopsies without fibrin deposition (n=5 P=0.02). Serum VEGF titers also were greater (P=0.01) in recipients with fibrin deposition (372.9+/-66.7 pg/ml n=18) compared to recipients without fibrin deposition (172.1+/-25.0 pg/ml n=16). Collectively, these results support the hypothesis that increased myocyte-derived VEGF production following microvascular fibrin deposition in transplanted human hearts may act in a paracrine manner to promote activational and phenotypic changes in capillaries that provide a survival advantage for the allografts.

Topics: Biopsy; Capillaries; Cell Hypoxia; Collateral Circulation; Diffusion; Endocardium; Endothelial Growth Factors; Enzyme-Linked Immunosorbent Assay; Fibrin; Gene Expression Regulation; Graft Survival; Heart Transplantation; Humans; In Situ Hybridization; Lymphokines; Myocardial Ischemia; Neovascularization, Physiologic; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Functional inhibition of tissue factor (TF) has been shown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P = 0.004) and 44% (P = 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P = 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R.

Topics: Animals; Antibodies, Monoclonal; Antithrombins; Cell Movement; Chemokines; Fibrin; Fibrinogen; Hirudins; Microscopy, Electron; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocarditis; Myocardium; Neutrophils; Rabbits; Thrombin; Thromboplastin

During episodes of dental bacteremia, viridans group streptococci encounter platelets. Among these microorganisms, certain Streptococcus sanguis induce human and rabbit platelets to aggregate in vitro. In experimental rabbits, circulating streptococci induced platelets to aggregate, triggering the accumulation of platelets and fibrin into the heart valve vegetations of endocarditis. At necropsy, affected rabbit hearts showed ischemic areas. We therefore hypothesized that circulating S. sanguis might cause coronary thrombosis and signs of myocardial infarction (MI). Signs of MI were monitored in rabbits after infusion with platelet-aggregating doses of 4 to 40 x 10(9) cells of S. sanguis 133-79. Infusion resulted in dose-dependent changes in electrocardiograms, blood pressure, heart rate, and cardiac contractility. These changes were consistent with the occurrence of MI. Platelets isolated from hyperlipidemic rabbits showed an accelerated in vitro aggregation response to strain 133-79. Cultured from immunosuppressed children with septic shock and signs of disseminated intravascular coagulation, more than 60% of isolates of viridans streptococci induced platelet aggregation when tested in vitro. The data are consistent with a thrombogenic role for S. sanguis in human disease, contributing to the development of the vegetative lesion in infective endocarditis and a thrombotic mechanism to explain the additional contributed risk of periodontitis to MI.

Topics: Animals; Bacteremia; Bacterial Physiological Phenomena; Blood Platelets; Blood Pressure; Cells, Cultured; Child; Coronary Thrombosis; Disseminated Intravascular Coagulation; Electrocardiography; Endocarditis, Bacterial; Fibrin; Heart Diseases; Heart Rate; Humans; Hyperlipidemias; Immunocompromised Host; Mouth; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Periodontitis; Platelet Aggregation; Rabbits; Shock, Septic; Streptococcus sanguis; Thrombosis