Intracoronary Thrombus Formation Research Articles

Prostacyclin analog maintains blood flow despite intracoronary thrombus formation in a canine model

Prostacyclin analog maintains blood flow despite intracoronary thrombus formation in a canine model

Intracoronary thrombus formation causes substantial vasoconstriction of human epicardial coronary arteries in vivo

Intracoronary thrombus formation causes substantial vasoconstriction of human epicardial coronary arteries in vivo

Urinary fibrinopeptide A levels in ischemic heart disease

Because acute coronary thrombosis can cause unstable coronary artery disease, fibrinopeptide A, a reliable marker of coagulation activity, may play a role in the evaluation of unstable Ischemic syndromes. A new method of fibrinopeptide A sampling, spot urine normalized to urinary creatinine, was evaluated in patients with stable and unstable angina pectoris and acute myocardial infarction. Serial samples were obtained to characterize the changes in urinary fibrinopeptide A levels over time in patients with Ischemic heart disease.Admission values (meanSD) were similar in the control group (3.3 ± 1.4 ng/mg creatinine) and the stable angina group (3.2 ± 1.1 ng/mg creatinine) (p = NS). Values in the unstable angina group (5.7 ± 2.6 ng/mg creatinine) were higher than those in the control (p = 0.008) and stable angina (p < 0.001) groups. Myocardial infarction admission values (8.4 ± 10.0 ng/mg creatinine) were higher than those in the control (p = 0.005) and stable angina (p < 0.001) groups, but not higher than those in the unstable angina group. Peak values (the highest of multiple samples) were higher in the unstable angina group (7.6 ± 5.9 ng/mg creatinine) than in the stable angina group (4.0 ± 1.0 ng/mg creatinine) (p = 0.04), but not in the control group (4.5 ± 1.9 ng/mg creatinine) (p = 0.056). The two patients with unstable angina with the highest peak values subsequently exhibited infarction. Peak values in patients with infarction (44.5 ± 60.0 ng/mg creatinine) were significantly higher than those in patients with unstable (p = 0.03) or stable (p = 0.002) angina and control patients (p < 0.001). urinary fibrinopeptide A levels were elevated in 10 (48%) of 21 unstable angina admission samples, 10 (53%) of 19 unstable angina peak samples, 6 (50%) of 12 myocardial infarction admission samples and 10 (91%) of 11 infarction peak samples. No patient with stable angina had an elevated urinary fibrinopeptide A value, and 2 of 12 control patients had a slightly elevated peak value.This study shows that spot urine fibrinopeptide A levels are elevated in virtually all patients with myocardial infarction and approximately half of the patients with unstable angina. Serial sampling demonstrates dynamic changes in fibrinopeptide A levels in patients with myocardial infarction, reflecting dynamic thrombin activity. Patients with unstable angina whose condition progresses to myocardial infarction have been shown to exhibit a similar dynamic tendency. Serial spot urinary fibrinopeptide A sampling, an easy method of sample acquisition, may be helpful in identifying those patients with unstable angina who have symptoms due to intracoronary artery thrombus formation and who are at the greatest risk of progressing to myocardial infarction.

Whole blood aggregation, thromboxane release and the lyso derivative of platelet activating factor in myocardial infarction and unstable angina.

To investigate the pathophysiology of intracoronary thrombus formation we measured whole blood aggregation in response to ADP, platelet activating factor (PAF) and collagen, along with thromboxane B2 (TXB2) production during collagen induced aggregation, plasma TXB2 and plasma levels of lyso-PAF, in 38 subjects with and without ischaemic heart disease (12 with acute myocardial infarction, 9 with prolonged ischaemic chest pain without infarction and 17 normals). Lyso-PAF was measured, after in vitro acetylation to active PAF, by bioassay using 14C-serotonin labelled rabbit platelets. TXB2 was measured by radioimmunoassay. Plasma TXB2 was elevated at presentation only in patients with myocardial infarction (p less than 0.01). While impedance aggregation was similar in the three groups, aggregation to collagen resulted in greater release of TXB2 in subjects with myocardial infarction (p less than 0.01), an abnormality persisting 2-4 months later. Plasma lyso-PAF levels were significantly depressed throughout the first week in subjects with infarction (p less than 0.002), but after 2 to 4 months the level was greater than in normal subjects (p less than 0.001), changes presently unexplained. It is possible that the disorder of platelet function preceded and predisposed to coronary thrombosis. The findings strengthen the grounds for aspirin therapy in acute myocardial infarction.

Local platelet activation causes vasoconstriction of large epicardial canine coronary arteries in vivo. Thromboxane A2 and serotonin are possible mediators.

The goal of the present study was to demonstrate that intracoronary platelet deposition may trigger intense vasoconstriction of large epicardial coronary arteries in vivo and that this is largely mediated by thromboxane A2 and serotonin released by activated platelets. Cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow) due to recurrent intracoronary platelet activation and thrombus formation were induced by damaging the endothelium and placing a cylindrical constrictor on the left anterior descending coronary artery (LAD) in open-chest, anesthetized dogs. Coronary diameters were measured in vivo by means of ultrasonic crystals sutured on the LAD immediately distal to the constrictor (LAD1) and 1 cm below (LAD2) and on the circumflex coronary artery (Cx). Coronary artery diastolic diameters were measured continuously before and during cyclic flow variations and after they were abolished by administration of LY53857, a serotonin-receptor antagonist (group 1, n = 7), or SQ29548, a thromboxane-receptor antagonist (group 2, n = 7). During cyclic flow variations, at the nadir of coronary flow, LAD1 (a site of maximal platelet accumulation) cross-sectional area decreased by 52 +/- 10% and 38 +/- 6% in group 1 and 2 animals, respectively (p less than 0.001 compared with values recorded during a brief LAD occlusion obtained by a suture snare), whereas LAD2 (a site of minimal or no platelet accumulation) cross-sectional area did not differ from that recorded during the brief LAD occlusion. SQ29548 abolished cyclic flow variations in seven of seven dogs and LY53857 in six of seven, but they affected the increased coronary vasoconstriction differently: LAD1 cross-sectional area increased by 32 +/- 6% of the control value in SQ29548-treated animals, whereas it returned to baseline dimension values in the LY53857-treated group as these interventions also abolished the cyclic flow variations. We conclude that a marked coronary vasoconstriction may be triggered by local platelet deposition and that thromboxane A2 and serotonin are mediators of this vasoconstriction.

Unstable angina: current concepts of medical management.

Unstable angina describes a clinical syndrome bridging the gap between stable angina and acute myocardial infarction. By definition, patients with angina of new onset, of a crescendo pattern, and with angina at rest are included in this high-risk group. The underlying pathogenetic mechanisms are complex and include initial atherosclerotic plaque rupture, release of vasoactive substances, and intracoronary thrombus formation. The currently established medical approach of the acute phase consists of heparin for anticoagulation and nitrates combined with beta-blockers for the relief of pain. Calcium antagonists are indicated, if anginal symptoms persist. The effect of thrombolytic therapy is still under investigation. Angina refractory to medical treatment and angina at rest are associated with a particularly unfavorable prognosis and prompt early catheterization. The long-term prognosis of the patient is markedly improved by chronic platelet inhibitory treatment with aspirin.

Effects of thrombolytic therapy in unstable angina: Clinical and angiographic results

The incidence of intracoronary thrombus and the effects of thrombolytic therapy were studied in 41 patients with unstable angina. All patients underwent coronary angiography 2 to 69 h (mean 19) after their last attack of chest pain. Immediately after angiography, 21 patients received intracoronary streptokinase (250,000 IU in 45 min) and were retrospectively analyzed. Twenty patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg in 3 h) and were involved in a prospective study.Eleven of the 21 patients from the streptokinase group and 11 of the 20 patients from the rt-PA group showed a decrease in the severity of the coronary stenosis on repeat angiography 1 day later. A decrease in coronary obstruction was primarily observed in 10 of 13 patient; with a complete stenosis and in 6 of 9 patients with a subtotal stenosis and markedly diminished coronary flow. Improvement in coronary anatomy was not determined by the clinical characteristics of the patients. Twenty-eight of the 41 patients had angiographic evidence of intracoronary thrombus formation before and 16 had such evidence after thrombolytic treatment. Nine patients developed a small increase in serum cardiac enzymes before or during treatment. Ischemic symptoms and the incidence of surgical or angioplastic intervention were not different in patients with or without a reduction in coronary artery stenosis after fibrinolytic therapy.These observations suggest a high incidence of coronary thrombosis in patients with unstable angina. The data do not permit assessment of the clinical therapeutic efficacy of thrombolylic therapy. Better risk stratification and placebo-controlled prospective studies are required to obtain information on the risk/benefit ratio of such therapy in unstable angina.

The role of intracoronary thrombus formation and thrombolytic treatment in acute myocardial infarction

The role of intracoronary thrombus formation and thrombolytic treatment in acute myocardial infarction

Intracoronary thrombus in nontransmural myocardial infarction and in unstable angina pectoris

Although intracoronary thrombus formation plays a major role in acute transmural myocardial infarction (MI), its occurrence in unstable angina (UA) and nontransmural MI has not clearly been established. To determine whether intracoronary thrombus does occur in these syndromes, coronary arteriography was performed before, during, and after intracoronary nitroglycerin and streptokinase infusion in 17 patients. None of the 8 patients with nontransmural MI and 1 of the 9 patients with UA responded to intracoronary nitroglycerin. Seven of 8 patients with nontransmural MI and 4 of 9 patients with UA responded to streptokinase infusion with opening of an occluded vessel, an increase in stenotic diameter, dissolution of an intracoronary filling defect, or a combination of these. Serial opening and closing of ischemia-related vessels occurred spontaneously and in response to streptokinase in some patients in whom thrombolysis was demonstrated. Evidence of thrombolysis was not seen in any patient studied longer than 1 week from the onset of the rest pain syndrome. The finding of thrombolysis in several patients with nontransmural MI and UA suggests that intracoronary thrombus formation plays a pathogenetic role in some patients with these ischemic syndromes.