Platelet inhibitory effect of nitric oxide in the human coronary circulation: impact of endothelial dysfunction.
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OBJECTIVES: We sought to determine whether coronary vascular nitric oxide (NO) release in vivo modulates platelet activation. BACKGROUND: Nitric oxide modulates vasodilator tone and platelet activity via the cyclic guanosine monophosphate (cGMP) pathway, but whether coronary endothelial dysfunction influences platelet activation in humans is unknown. METHODS: In 26 patients, we measured coronary blood flow, epicardial diameter and coronary sinus platelet cGMP content during intracoronary infusions of acetylcholine (ACH), L-NG monomethyl arginine (L-NMMA) and sodium nitroprusside. RESULTS: Acetylcholine increased platelet cGMP content (p = 0.013), but its magnitude was lower in patients with endothelial dysfunction; thus, patients with epicardial constriction with ACH had a 7 +/- 6%, p = ns change compared with a 32 +/- 13%, p = 0.05 increase in platelet cGMP in those with epicardial dilation. Similarly, patients with atherosclerosis or its risk factors had a smaller increase (9 +/- 6%) compared with those having normal coronary arteries without risk factors (51 +/- 22%, p = 0.019). L-NG monomethyl arginine decreased platelet cGMP content to a greater extent in patients with epicardial dilation with ACH (- 15 +/- 7%, p = 0.06) compared to those with constriction (+5 +/- 6% change, p = 0.5). Sodium nitroprusside produced a similar increase in platelet cGMP content in patients with and without endothelial dysfunction (p = 0.56). The effects of sodium nitroprusside, but not ACH or L-NMMA, were reproduced in vitro. CONCLUSIONS: Platelet cGMP levels can be modulated by basal and stimulated release of NO. The platelet inhibitory effect of NO is reduced in patients with endothelial dysfunction, which may explain their increased risk from thrombotic events and the improved survival associated with strategies designed to improve vascular function. (+info)
A safe and effective regimen without heparin therapy after successful primary coronary stenting in patients with acute myocardial infarction.
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Short-term heparin therapy has been administered routinely after primary coronary stenting. However. heparin therapy results in a significantly higher incidence of bleeding and vascular complications. A new therapeutic regimen of ticlopidine and aspirin without further heparin after coronary stenting in patients without AMI has been shown to be safe and reduce the incidence of stent thrombosis. The aim of this study was to evaluate whether a new therapeutic regimen of aspirin and ticlopidine without heparin is safe and effective in patients with acute myocardial infarction (AMI) who have undergone primary coronary stenting and have Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery. Between January 1997 and September 1999, one hundred and fifty two consecutive patients with AMI on Killip score 1 or 2 who underwent primary coronary stenting resulting in TIMI grade 3 flow were enrolled and divided into two groups: Group 1 (n = 95 patients) received aspirin, ticlopidine and further intravenous heparin infusion for 48 hours following primary coronary stenting; Group 2 (n = 57 patients) received only aspirin and ticlopidine without further heparin therapy following primary coronary stenting. No in-hospital major cardiac events were observed in either group. However, the combined incidence of bleeding and vascular complications (27.4% vs 12.3%, p = 0.029) and the need for blood transfusions (9.5% vs 0%, p = 0.013) were significantly higher in Group I patients. Furthermore, hospital stay was also longer in Group I patients (5.8+/-2.4 vs 4.7+/-1.7 days, p = 0.0003). At the 30-day follow-up, there were no differences (1.05% vs 0%, p = 0.63) in the combined incidence of vascular complications and the major cardiac events were similar (1.05% vs 1.75%, p = 0.71) between the groups. The results suggest that further heparin therapy following primary coronary stenting increases the combined incidence of bleeding and vascular complications as well as the need for blood transfusions and prolongs the length of hospital stay without further benefit to those patients with coronary flow restored to TIMI 3 grade flow. (+info)
A case of acute myocardial infarction: intracoronary thrombus formation at a previously provoked vasospasm site.
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A 58-year-old Japanese man with variant angina developed acute myocardial infarction (AMI). Emergency coronary angiography demonstrated thrombotic occlusion in the proximal site of the left anterior descending artery. The occluded region appeared to be coincident with the area in which severe vasospasm had been provoked by intracoronary administration of acetylcholine 1.5 years before the onset of AMI. This case may give us a unique opportunity to consider the role of vasospasm in the etiology of AMI. (+info)
Thrombosis in one coronary artery causes generalized coronary vasoconstriction in a dog model of unstable angina.
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We investigated the effect of thrombosis in one coronary artery upon the vascular resistance of another coronary artery. In previous investigations, using an animal model of unstable angina, we have observed increased resistance downstream from thrombus within a left circumflex coronary artery (LCx) stenosis and vasoconstriction of collateral vessels from the left anterior descending artery (LAD) supplying the distal LCx vascular bed. In the present paper, we induced thrombosis within a stenosis of the LCx of 16 beagle dogs, and observed the changes in blood flow to the myocardium supplied by the LAD using the radioactive microsphere technique. This blood flow decreased with thrombosis (P = 0.005) in these animals, whereas it did not do so in three time-control experiments. The pressures across the coronary vascular bed, i.e. arterial pressure to coronary venous pressure (coronary sinus catheter), did not change. Thus the vascular resistance of the LAD bed increased significantly from 147 +/- ll.5 mmHg/ml/sec/g of tissue to 172 +/- 13.4 mmHg/ml/sec/g of tissue (P = 0.02). As the LAD territory is not perfused with blood from the artery containing thrombus, we conclude that the effect observed is caused either by release of vasoconstrictors from the thrombus into the general circulation, or by activation of a neural reflex vasoconstriction. The study suggests that unstable angina involving thrombosis in one coronary artery is a global coronary vascular disease. (+info)
Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis.
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BACKGROUND: The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart. METHODS AND RESULTS: After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 microgram/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5+/-0.8 mm(3)/mm vessel (range 0.6 to 13.7 mm(3)/mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (P<0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (P<0.006 for both). There was a strong inverse correlation between the LAD plaque burden and release of active tPA (r=-0.61, P=0.003). Cigarette smoking was associated with impaired coronary release of active tPA (current smokers, 31+/-23 IU/min; ex-smokers, 50+/-33 IU/min; nonsmokers 202+/-73 IU/min; P<0.05). CONCLUSIONS: We found that both the coronary atheromatous plaque burden and smoking habit are associated with a reduced acute local fibrinolytic capacity of the heart. These important findings provide evidence of a direct link between endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the coronary circulation and may explain the greater efficacy of thrombolytic therapy for myocardial infarction in cigarette smokers. (+info)
Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials.
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BACKGROUND: There are limited studies of stent thrombosis in the modern era of second-generation stents, high-pressure deployment, and current antithrombotic regimens. METHODS AND RESULTS: Six recently completed coronary stent trials and associated nonrandomized registries that enrolled 6186 patients (6219 treated vessels) treated with >/=1 coronary stent followed by antiplatelet therapy with aspirin and ticlopidine were pooled for this analysis. Within 30 days, clinical stent thrombosis developed in 53 patients (0.9%). The variables most significantly associated with the probability of stent thrombosis were persistent dissection NHLBI grade B or higher after stenting (OR, 3.7; 95% CI, 1.9 to 7.7), total stent length (OR, 1.3; 95% CI, 1.2 to 1.5 per 10 mm), and final minimal lumen diameter within the stent (OR, 0.4; 95% CI, 0.2 to 0.7 per 1 mm). Stent thrombosis was documented by angiography in 45 patients (0.7%). Clinical consequences of angiographic stent thrombosis included 64.4% incidence of death or myocardial infarction at the time of stent thrombosis and 8.9% 6-month mortality. CONCLUSIONS: Stent thrombosis occurred in <1.0% of patients undergoing stenting of native coronary artery lesions and receiving routine antiplatelet therapy with aspirin plus ticlopidine. Procedure-related variables of persistent dissection, total stent length, and final lumen diameter were significantly associated with the probability of stent thrombosis. Continued efforts to eliminate this complication are warranted given the serious clinical consequences. (+info)
Invasive pulmonary aspergillosis with thrombosis in the left atrium.
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We report a female patient with left atrial wall invasion from pulmonary aspergillosis. She had been treated for diabetes mellitus. Pulmonary aspergillosis extended to the left atrial wall via the left pulmonary vein and formed a polypoid lesion in the left atrium. The polypoid lesion was composed of thrombus, and the thrombus increased in size to become large, and it showed invagination into the mitral valve during diastole. We considered that the thrombus was formed on the injured endocardium. Severe invasive aspergillosis thus could occur in a mild systemic immunocompromised host. (+info)
Combined revascularization strategy for acute myocardial infarction in patients with intracoronary thrombus: preceding intracoronary thrombolysis and subsequent mechanical angioplasty.
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Thrombus in the infarct-related artery is one of the limitations for flow restoration in primary percutaneous transluminal coronary angioplasty (PTCA) treatment for acute myocardial infarction (AMI). The present study investigated the benefit of preceding intracoronary thrombolysis (ICT) by retrospectively analyzing acute phase flow restoration in 80 AMI patients with intracoronary thrombus: 40 undergoing primary PTCA alone (primary PTCA group) and 40 treated with preceding ICT plus PTCA (combined group). Acute phase Thrombolysis in Myocardial Infarction (TIMI) grade flow was as follows: TIMI 0/1: 35.0% vs 12.5% for the primary PTCA group and the combined group, p=0.06; TIMI 2: 7.5% vs 15.0%, p=NS; TIMI 3: 57.5% vs 72.5%, p=NS). In the subgroup analysis, it was also less in the combined group among 33 patients with a left anterior descending coronary artery (LAD) lesion (42.1 % vs 7.1%, p=0.08), but not among the remaining 47 with either a right coronary artery or left circumflex artery lesion. The combined therapy may potentially provide better acute phase flow restoration in AMI patients with an intracoronary thrombus in a LAD lesion. (+info)