PubMed Health⌕ Search

Biomedical subjects

J H Chesebro

Publications and source records attributed to J H Chesebro.

At least 163 records · Page 9Linked to original sources
PubMed1986

Role of antithrombotic therapy in unstable angina, myocardial infarction and sudden death.

The role of platelets and the clotting system in the initiation and progression of atherosclerosis has received significant attention. Most importantly, platelets and thrombosis play a pivotal role in the pathogenesis of the acute coronary syndromes of unstable angina, myocardial infarction and sudden death. In each stage of the development of coronary artery disease, from the early symptomatic stage through the growing lesion and finally to the complicated plaque that results in the precipitation of the acute coronary syndromes, platelets and the clotting system serve as a common link among them. Antithrombotic therapy aimed at halting the progression of these syndromes, preventing their occurrence or even reversing them (such as in the early stages of acute myocardial infarction), has provided exciting new modalities to treat these disorders. The use of aspirin in unstable angina in two well designed studies has clearly shown a reduction in fatal as well as nonfatal cardiac events compared with control groups not treated with aspirin. Although demonstration of a benefit of anticoagulant and antiplatelet therapy is difficult owing to a low event rate of thrombotic events (low sensitivity) and other nonthrombotic fatal events (low specificity) after myocardial infarction, pooled results have shown a favorable effect with their use. The usefulness of thrombolytic therapy in the early stages of acute myocardial infarction depends on the timing of initiation of therapy, the severity of the residual stenosis and possible use of agents that protect the ischemic myocardium. Other potential therapies for the acute coronary syndromes are also suggested. Further studies are in progress to establish the clinical benefits of antithrombotic agents in acute coronary syndromes.

Anticoagulants↗
PubMed1986

Thrombosis and embolism from cardiac chambers and infected valves.

In a number of cardiac conditions (acute myocardial infarction, chronic left ventricular aneurysm, dilated cardiomyopathy, infective endocarditis and atrial fibrillation in the absence of valvular disease), the risk of embolism gives cause for concern. Although anticoagulation with warfarin (Coumadin)-derivatives has been shown to be effective in some of these situations, there is no evidence regarding the role of antiplatelet agents. The common factor in the thromboembolic potential of acute myocardial infarction, chronic left ventricular aneurysm and dilated cardiomyopathy is mural thrombus. This can be detected by two-dimensional echocardiography and indium-111 platelet scintigraphy. Although of value in elucidating the natural history of mural thrombus, in most cases, management is not substantially aided by these investigations. In patients with extensive myocardial infarction, particularly anterior infarction, moderate intensity anticoagulation started soon after hospital admission reduces the rate of embolism. After 8 to 12 weeks, embolic risk is low so that anticoagulants can usually be discontinued. Patients with chronic left ventricular aneurysm have a low incidence of embolism; anticoagulation is, therefore, inappropriate. Dilated cardiomyopathy is associated with a high risk of embolism; moderate intensity anticoagulation may be advisable in many such cases. Little information is available regarding the incidence of thromboembolism or the role of antithrombotic therapy in the patient with a diffusely dilated left ventricle due to ischemic heart disease. In native valve infective endocarditis, the risk of hemorrhage is high, and the efficacy of conventional anticoagulants unclear; thus, anticoagulation should not be instituted for the cardiac condition as such. However, in prosthetic valve endocarditis, the risk of embolism seems to be very high, and anticoagulant therapy should be continued, but with great care because there is a substantial risk of cerebral hemorrhage. Atrial fibrillation in patients with valvular heart disease is dealt with in a previous review. Patients with nonvalvular atrial fibrillation are at varying risk of embolism, depending on the etiology of the arrhythmia; trials of antithrombotic therapy are needed for the various subsets of patients. In most elderly patients, the etiology is not known, and their stroke risk is high. The risk of embolism in younger patients with idiopathic atrial fibrillation is so low as to make any antithrombotic therapy unnecessary.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticoagulants↗
PubMed1986

Deep arterial injury during experimental angioplasty: relation to a positive indium-111-labeled platelet scintigram, quantitative platelet deposition and mural thrombosis.

Although it is not clear why coronary occlusion and restenosis occur after successful coronary angioplasty, factors related to the procedure may influence early and late results. The possible adverse effects of a medial tear documented histologically and produced during balloon angioplasty of the common carotid arteries were studied in 30 fully heparinized (100 U/kg body weight) normal pigs. Scanning electron microscopy showed endothelial denudation and extensive platelet deposition in all dilated arterial segments. Visible macroscopic mural thrombus was present within an hour of the procedure in 29 (91%) of the 32 arteries that had a medial tear documented by histologic study; the tear produced an indium-111-labeled platelet deposition of 116.4 +/- 26.5 X 10(6)/cm2 (mean +/- SE) and total thrombotic occlusion in 2 arteries (4%). None of the 24 arteries without a medial tear had a thrombus, and the mean platelet deposition in that group was 7.0 +/- 0.5 X 10(6)/cm2 (p less than 0.0008). In 12 pigs scanned with a gamma camera, visible thrombus was associated with platelet deposition in excess of 20 X 10(6)/cm2 in 12 arteries, 9 of which had a positive indium-111-labeled platelet scintigram. Thus, arterial angioplasty causes deep arterial injury, which appears to be a major cause of mural thrombosis, heavy platelet deposition, a positive indium-111-labeled platelet scintigram and acute arterial occlusion. A positive indium-111-labeled platelet scintigram was always associated with macroscopic thrombus of at least 20 > 10(6) platelets/cm2 and underlying deep arterial injury.

Angioplasty, Balloon↗
PubMed1986

Evaluation of antiplatelet agents in the prevention of aorto-coronary bypass occlusion.

The cumulative occlusion rates of aorto-coronary artery venous bypass grafts average from 16 to 26% per distal anastomosis within 12 months and about 2% per following year. The potential benefit of oral anticoagulants and platelet inhibitor drugs has been tested to prevent graft occlusion and to retard the atherosclerotic process. Oral anticoagulants started on the third postoperative day do not significantly reduce graft occlusion after 6 months. Among the platelet inhibitor drugs, dipyridamole started before surgery, followed by dipyridamole and aspirin soon after surgery, was the drug regimen with the best results. More randomised double-blind clinical trials are highly desirable to confirm these findings and to resolve the question of relative efficacy and safety for the various drugs reported to have shown benefit when used in combination.

Administration, Oral↗
PubMed1986

Platelet-inhibitor drugs before and after coronary artery bypass surgery and coronary angioplasty: the basis of their use, data from animal studies, clinical trial data, and current recommendations.

The pathogenesis of aortocoronary vein-graft occlusion appears to be similar to the development of atherosclerosis, except that it is more accelerated, especially during the first postoperative year. Initiation of platelet-inhibitor therapy before operation is important especially in patients at high risk of bypass graft occlusion because platelet deposition starts during operation and initiates the process of occlusion. The largest and only placebo-controlled trial to start therapy before operation showed that dipyridamole (Persantine) plus aspirin markedly reduced occlusion (compared with placebo) in both high- and low-risk subgroups both early and at a median of 1 year after operation. Arterial balloon angioplasty often causes severe arterial wall injury, which is a potent stimulus for immediate platelet-thrombus deposition and is probably the main contributing factor in the process of restenosis. Animal studies suggest the potential value of antithrombotic therapy starting the day before the angioplasty procedure, but results from placebo-controlled trials in humans are needed before optimal therapy can be established.

Angioplasty, Balloon↗
PubMed1986

Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease.

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we conducted a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun 2 days before operation) plus aspirin (begun 7 hr after operation) with placebo in 407 patients. Results at 1 month and at 1 year showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. On the basis of our clinical trial and our experimental studies in dogs and pigs, we describe four consecutive phases of aortocoronary artery bypass vein-graft disease: an early postoperative phase of platelet thrombotic occlusion, which is significantly prevented by platelet inhibitor therapy when started in the perioperative period; in addition, occlusion rates are presently decreasing, perhaps related to better surgical and technical experience; an intermediate phase of platelet-related intimal hyperplasia, within the first postoperative year, which is not prevented with platelet inhibitor therapy; a late phase of occlusion, toward the end of the first postoperative year, in which intimal hyperplasia or complicating platelet thrombi superimposed on the intimal hyperplasia may contribute to occlusion; platelet inhibitor therapy is of significant benefit in the prevention of this thrombotic type of occlusion; a phase of atherosclerotic disease, after the first postoperative year, in which the role of platelets and of platelet inhibitor therapy is under investigation.

Animals↗
PubMed1986

Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction: a report from the NHLBI thrombolysis in myocardial infarction trial.

The efficacy and safety of a 3 hr, 80 mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 47 patients with acute myocardial infarction. Coronary angiography, performed before the administration of rt-PA and for 90 min thereafter, demonstrated that 37 patients had total coronary occlusion before therapy. After 90 min of rt-PA (50 mg), reperfusion of the infarct-related artery was observed in 25 patients (68%). Continuous infusions of heparin for anticoagulation were administered for 8 to 10 days. Of 36 patients who underwent follow-up coronary cineangiography, 21 had initially presented with total occlusion and had experienced reperfusion at 90 min. Sustained perfusion of the infarct-related artery was observed in 14 (67%) of these 21 initially reperfused patients. Late angiography was performed in nine patients who initially demonstrated subtotal occlusion of the infarct-related artery; sustained perfusion was observed in eight (89%). Significant bleeding was observed in 15 patients (32%). A hematoma at the site of the acute catheterization accounted for most instances of significant bleeding (11/15, 73%). Administration of rt-PA resulted in a significant decline in fibrinogen and plasminogen while amounts of fibrin(ogen) degradation products rose. In no patient, however, did fibrinogen levels decline to less than 140 mg/dl. Thus, rt-PA, administered as a brief 80 mg intravenous infusion, is capable of restoring blood flow in a high proportion of patients with acute myocardial infarction due to total coronary obstruction. Declines in plasma fibrinogen and plasminogen are observed. If combined with heparin anticoagulation and invasive vascular procedures, significant bleeding is a common complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Quantification of regional platelet and calcium deposition on pericardial tissue valve prostheses in calves and effect of hydroxyethylene diphosphonate.

Mitral valves were replaced with 25 mm bovine pericardial tissue valve prostheses (Ionescu-Shiley) in 45 calves (23 controls and 22 treated daily with hydroxyethylene diphosphonate). Before being killed 1, 14, 30, and 90 days later, the calves received In-labeled autologous platelets intravenously. Regional variations in platelet deposition were measured by a new technique. Thrombus was noted early on the flexion zone of the valve; with time it increased on the free edge and central zone. Platelet deposition was initially high on the flexion zone, attachment zone, sewing ring, and perivalvular tissue but decreased with time. Hydroxyethylene diphosphonate treatment tended to decrease platelet deposition in all zones. Calcium content was high in thrombus and increased in all zones with time, in both groups, but the deposition was less in the group treated with hydroxyethylene diphosphonate. Collagenous tissue and adherent thrombus appear to provide nucleation sites for calcification.

Animals↗
PubMed1986

Pathogenesis and prevention of aortocoronary bypass graft occlusion.

Aortocoronary bypass graft occlusion starts intraoperatively, is progressive over time, and correlates with the return of ischaemic symptoms and left ventricular dysfunction during exercise. Based on an animal model and tests of in vivo platelet consumption and deposition, a prospective, randomized, double-blind trial was designed and carried out comparing dipyridamole (instituted two days before operation plus aspirin (added seven hours after operation) with a placebo in 407 patients. Vein-graft angiography was performed in 88% of patients early after operation. Within 4-6 months of operation, 4% of 488 distal anastomoses were occluded in the treated patients and 15% of 520 distal anastomoses were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 10% of 176 patients in the treated group and 30% of 184 patients in the placebo group (p = 10(-6)). Unlike other less convincing studies that did not start therapy before operation and did not affect high risk subgroups, benefit in graft patency in this study persisted in each of over 50 subgroups of high and low risk. Perioperative bleeding was similar in the two groups. Late after operation (11-18 months, median 12 months), 11% of 478 vein-graft distal anastomoses were occluded in the treated group, and 25% of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22% of 171 patients in the treated and 47% of 172 patients in the placebo group (p = 10(-6)).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗
PubMed1985

Percutaneous transluminal coronary angioplasty, alone or in combination with streptokinase therapy, during acute myocardial infarction.

The treatment strategy in 66 consecutive patients who underwent invasive therapy for acute myocardial infarction was analyzed, and specific attention was focused on the role of percutaneous transluminal coronary angioplasty. The following four treatment regimens were used: angioplasty alone (11 patients), angioplasty followed immediately by administration of streptokinase (15), streptokinase therapy alone (11), and streptokinase therapy followed by angioplasty (29). Reperfusion was achieved in 91%, 80%, 82%, and 72% of these subgroups, respectively. Angioplasty was particularly helpful in patients with severe residual stenoses after intracoronary administration of streptokinase and in patients in whom streptokinase therapy failed to reopen the occluded artery. Angioplasty further reduced the residual stenosis in 11 of 15 patients (73%) with successful thrombolysis, and it restored blood flow in 10 of 14 patients (71%) in whom thrombolysis had failed to do so. The incidence of reinfarction after therapy was similar in all four treatment groups. Patients in whom angioplasty was used either alone or in combination with streptokinase therapy had a significantly decreased incidence of subsequent revascularization (less than 30% compared with 82%). Angioplasty is of considerable value in patients undergoing invasive therapy for acute infarction. In some patients, it may be used as the only treatment; in others, it may be used to treat severe residual stenosis after initial streptokinase therapy. Finally, angioplasty achieves reperfusion in most patients in whom streptokinase therapy has failed.

Adult↗
PubMed1985

Intracoronary thrombus: role in coronary occlusion complicating percutaneous transluminal coronary angioplasty.

Angiograms from 238 consecutive patients who underwent percutaneous transluminal coronary angioplasty at the Mayo Clinic were reviewed to determine the presence of intracoronary thrombus before dilation. Patients with previously occluded vessels and those receiving streptokinase therapy were excluded. Intracoronary thrombus before dilation was present in 15 patients (6%); complete occlusion occurred in 11 (73%) of these during or immediately after dilation. None of these patients had angiographic evidence of major intimal dissection. In contrast, among the 223 patients in whom no intracoronary thrombus was present before dilation, complete occlusion occurred in 18 (8%) and in 12 was associated with major intimal dissection. The difference between the complete occlusion rates for patients with and without prior intracoronary thrombus was highly significant (73 versus 8%, respectively, p less than 0.001). Therefore, the presence of intracoronary thrombus identifies a group of patients who are at increased risk of developing complete occlusion during or after attempted coronary artery dilation.

Acute Disease↗
PubMed1985

Systemic embolism in chronic left ventricular aneurysm: incidence and the role of anticoagulation.

The incidence and prevention of systemic embolism in patients with chronic left ventricular aneurysm have been controversial. This retrospective study investigated the incidence of clinically evident embolic events and the effect of oral anticoagulation in patients with unequivocal angiographically defined left ventricular aneurysm. Between 1971 and 1979, 76 patients met the ventriculographic criteria and received initial medical management. The median interval from myocardial infarction to ventriculography was 11 months (range 1 month to 16 years) and subsequent median follow-up time was 5 years. Twenty patients receiving anticoagulant therapy were followed up for a total of 40 patient-years and 69 patients not on anticoagulant therapy were followed up for a total of 288 patient-years; 13 patients were included in both subsets. Twenty-eight patients died during follow-up and the 3 and 5 year survival rates were 75 and 61%, respectively. Only one patient not receiving anticoagulant therapy had a clinical embolic event, resulting in an incidence of 0.35 per 100 patient-years. Therefore, in the absence of other predisposing conditions, the extremely low incidence of systemic emboli in these patients with chronic (first documented at least 1 month after myocardial infarction) left ventricular aneurysm does not justify the use of long-term oral anticoagulant therapy.

Adult↗
PubMed1985

High dose intravenous streptokinase for acute myocardial infarction: preliminary results of a multicenter trial.

To assess the efficacy of intravenous streptokinase in patients with acute myocardial infarction, 40 patients (30 men and 10 women, mean age 54 years) with acute myocardial infarction were given 1.5 million U of streptokinase intravenously in 1 hour, and coronary arteriography was performed repeatedly to assess reperfusion. Streptokinase treatment was begun 270 +/- 86 (mean +/- SD) minutes after the onset of chest pain. Of the 40 patients, 34 had total or near total coronary occlusion before streptokinase administration. In 14 (41%) of these 34 patients, some reperfusion occurred during the 90 minutes after the administration of streptokinase, but in only 11 of the 14 was reperfusion present at 90 minutes. After streptokinase administration, all patients received heparin for 8 to 10 days; they were subsequently administered aspirin and dipyridamole. Clinical evidence of reocclusion during the first 24 hours of heparin therapy occurred in one patient. Thus, when given to patients with acute myocardial infarction and total coronary occlusion an average of 4 1/2 hours after the onset of chest pain, high dose intravenous streptokinase achieves reperfusion in only about 40% and results in sustained reperfusion in only about 30%.

Adult↗
PubMed1985

Role of platelets and thrombosis in coronary atherosclerotic disease and sudden death.

During the last decade, significant advances have been made in the understanding of the pathogenesis of coronary atherosclerotic disease. Two facts are important: 1) the early and some of the advanced coronary atherosclerotic lesions progress very slowly, probably by means of a complex stepwise biologic process with one of the steps being an interaction between platelets and the arterial wall; the process can be favored by the so-called risk factors of atherosclerotic disease, and 2) some of the advanced coronary atherosclerotic lesions progress very rapidly, probably by means of complicating anatomic events, one of which is related to a thrombogenic process. From a clinical point of view, technologic improvements, such as serial coronary arteriography, reperfusion during the acute coronary artery syndromes, postmortem coronary arteriography, and methods for serial histopathologic and histochemical studies, have brought to light the clinical importance of the processes of plaque rupture, dissecting hemorrhage and, most important, thrombosis. These complicated processes appear to be of paramount importance in the pathogenesis of some of the acute coronary syndromes including unstable angina, myocardial infarction and sudden coronary death. Antithrombotic and platelet inhibitor therapy is under investigation and appears promising in some of these patient subsets.

Angina, Unstable↗
PubMed1985

Platelet-inhibitor therapy in cardiovascular disease. Effective defense against thromboembolism.

Platelet deposition can occur in areas of vascular damage and on prosthetic materials such as heart valves or grafts; mural thrombus formation, with eventual organization, progression to fatal occlusion, thrombolysis, or arterial embolization can follow. Use of antiplatelet drugs in patients undergoing certain cardiovascular surgical procedures or having rapid progression of atherosclerosis may reduce the thromboembolic risk.

Angioplasty, Balloon↗
PubMed1985

Intracardiac thrombi and systemic thromboembolism: detection, incidence, and treatment.

The detection of thrombus in the left atrium is discussed in this chapter, along with the problem of arterial thromboembolism in patients with valvular heart disease and prosthetic heart valves. The detection and occurrence of thrombus within the left ventricle are considered, as is the frequency of thromboembolism in acute myocardial infarction, left ventricular aneurysm, and cardiomyopathy. Treatment recommendations are given for each of these medical problems.

Anticoagulants↗
PubMed1985

Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model.

The restenosis or occlusion that frequently follows balloon angioplasty is poorly understood. Thus, the pathophysiological response to angioplasty of the common carotid artery in 38 heparinized normal pigs was investigated by quantification of the 111In-labeled platelet deposition and histological and electron microscopic examination from 1 hour to 60 days after angioplasty. At 1 hour, the following findings were noted: complete endothelial denudation in all arteries, marked platelet deposition (44.7 +/- 20.7 X 10(6)/cm2), mural thrombus in seven of 10 pigs, and a medial tear extending through the internal elastic lamina in nine of 18 arteries. All nine arteries with tears had associated mural thrombus and severe platelet deposition (76 X 10(6)/cm2); in contrast, the nine arteries without a tear had no mural thrombus and much lower platelet deposition (6 X 10(6)/cm2). Necrosis of medial smooth muscle cells was evident at 24 hours. Platelet deposition remained high at 24 hours (40.5 +/- 20.6 X 10(6)/cm2), but was markedly reduced at 4 days (4.4 +/- 1.5 X 10(6)/cm2), coincident with partial regrowth of endothelium or periluminal lining cells. No significant platelet deposition was noted at 7 days, when the endothelial cell type of regrowth was largely complete. Intimal proliferation of smooth muscle cells was mild and patchy at 7 days, significantly greater and more uniform at 14 days, and unchanged at 30 and 60 days after angioplasty. Complete thrombotic occlusion occurred in four (11%) of the 38 pigs. A significant stenosis present at 30 days after angioplasty was shown by histological examination to be due to organization of mural thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗