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Biomedical subjects

J H Chesebro

Publications and source records attributed to J H Chesebro.

At least 127 records · Page 7Linked to original sources
PubMed1990

Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

Aged↗
PubMed1990

Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis.

Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quantitative indium-111-labeled platelet and iodine-125-labeled fibrinogen deposition and the incidence of mural thrombosis. This study showed that heparin, at a dose that prolonged the activated partial thromboplastin time (APTT) to twice the control time, did not prevent mural thrombosis or significantly reduce platelet deposition compared with placebo but did reduce fibrinogen deposition. Recombinant hirudin markedly reduced platelet and fibrinogen deposition in a dose-related manner and totally eliminated mural thrombosis at an APTT of two to three times that of control. Platelet deposition (x 10(6)/cm2, mean +/- SEM) in areas of deep arterial injury for the placebo, heparin, and 0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8 +/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer (or less) of platelets at the two highest hirudin dosages. The incidence of macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46% with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Platelet inhibitor therapy. Agents and clinical implications.

Platelets are central to the pathophysiology of an array of vascular disorders. Current platelet-inhibitor drugs reduce platelet aggregation through one of three pathways but do not prevent initial platelet adhesion. The most extensive clinical experience is with aspirin, an irreversible inhibitor of cyclooxygenase. Aspirin is clinically effective and has few gastrointestinal side effects if used at a dosage of 150 to 300 mg per day. Large clinical trials have documented the benefits of aspirin in arterial thromboembolic disease. It is effective in the primary and secondary prevention of myocardial infarction, including patients with unstable angina; reduces the acute thrombotic complications of coronary angioplasty and revascularization surgery; and also reduces cerebral ischemic events in patients with cerebrovascular disease. Aspirin is less effective for thrombi arising from the venous system or intracardiac chambers, which respond well to anticoagulants. Dipyridamole and sulfinpyrazone are most effective at preventing thrombosis on prosthetic surfaces. Dipyridamole reduces emboli from mechanical prosthetic valves when combined with warfarin and, unlike aspirin plus warfarin, does not increase bleeding complications. Newer agents such as ticlopidine and the thrombin inhibitor, hirudin, appear promising but require further evaluation. Because thrombin plays a critical role in mechanisms of arterial thrombosis, its inhibition appears promising for future therapy.

Adult↗
PubMed1990

Atherosclerotic plaque rupture and thrombosis. Evolving concepts.

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.

Acute Disease↗
PubMed1989

Effects of acute reperfusion on regional myocardial function: serial two-dimensional echocardiography assessment.

Serial two-dimensional echocardiography was performed in 23 patients with acute myocardial infarction who received intravenous thrombolytic therapy to evaluate the effect of acute reperfusion on regional wall motion abnormalities. Regional wall motion abnormalities improved in 4 of the 14 patients (29%) with successful reperfusion and in 1 of the 9 (11%) without successful reperfusion. In successfully reperfused patients, the main determinant of improvement in regional wall motion abnormalities was duration from the onset of chest pain to the time of reperfusion (3.3 vs. 6.3 h in successfully reperfused patients without recovery of regional wall motion abnormalities; P less than 0.001).

Adult↗
PubMed1989

Platelet inhibitor agents in cardiovascular disease: an update.

Platelets interact with the coagulation and fibrinolytic systems in the maintenance of hemostasis. However, these physiologic mechanisms may become pathologic, requiring prevention and treatment. In this review, the following clinical developments are analyzed: 1) the role of platelets in thrombogenesis; 2) the pharmacology of platelet inhibitory agents; and, most important, 3) the results of recent randomized trials of platelet inhibitor agents in different cardiovascular disorders. Aspirin reduces mortality and infarction rates in unstable angina and significantly decreases vascular mortality in acute myocardial infarction. Platelet inhibitors decrease mortality and recurrent cardiovascular events in the chronic phase after myocardial infarction. They also decrease vein graft occlusion rates after coronary bypass surgery. Although platelet inhibitors are beneficial in preventing acute vessel occlusion during coronary angioplasty, they are ineffective in preventing chronic restenosis. Antiplatelet agents, combined with warfarin, reduce thromboembolic events in patients with a mechanical prosthesis. Platelet inhibitors are also effective in secondary prevention of vascular events in patients with cerebrovascular disease. Finally, the use of aspirin for primary prevention of cardiovascular disease is still evolving, particularly in individuals at high risk. In conclusion, platelet inhibitors are effective in patients with a variety of cardiovascular disorders. The best studied, most inexpensive and least toxic agent is aspirin at a daily dose of 160 to 325 mg. Studies using new platelet inhibitor agents with different mechanisms of action are currently underway.

Aspirin↗
PubMed1989

Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor.

The effect of recombinant hirudin and the dosage of heparin on acute platelet-thrombus deposition during carotid angioplasty in anesthetized pigs was prospectively assessed. Fifty-five animals (mean weight, 33.9 kg) were randomized to one of six heparin dosages: heparin boluses of 35, 50, 100, 150, 200, or 250 units/kg followed by a continuous infusion of 35, 50, 100, 150, 200, or 250 units/kg/hr, respectively. Another five pigs received a bolus of 1 mg/kg hirudin (recombinant desulphatohirudin), a specific thrombin inhibitor, followed by an infusion of 1 mg/kg/hr. Bilateral carotid angioplasty was performed in all pigs 20 minutes after starting the infusion; they were sacrificed 57 +/- 12 minutes after the procedure. Deep medial arterial injury was present in approximately 75% of the dilated segments, and subendothelial injury in the remaining 25%. Mean log of number of platelets and molecules of fibrinogen per centimeter squared of deep injury in segments from all the animals treated with heparin were 4.74 +/- 1.03 and 5.02 +/- 0.64, respectively. A regression analysis showed an inverse correlation of the log of platelet deposition with the heparin group (r = -0.56, p = 0.0001) with administered total units of heparin (r = -0.55, p = 0.0003) and with mean plasma heparin concentration (r = -0.55, p = 0.0004) in deeply injured arteries. Similar inverse relations were obtained for fibrinogen. In contrast, the deposition of platelets and fibrinogen in subendothelial injury was very low and independent of the heparin administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1989

Feasibility of tomographic 99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction.

99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-Sestamibi), a new myocardial perfusion radiopharmaceutical, was injected intravenously in 11 patients within 4 hours of the onset of acute myocardial infarction before treatment with intravenous tissue-type plasminogen activator and 6-14 days later. Five patients with acute myocardial infarction who did not receive intravenous thrombolytic therapy underwent a similar injection of radiopharmaceutical. The absence of redistribution of Tc-Sestamibi permitted imaging with single-photon emission computed tomography up to 6 hours after intravenous injection to assess the distribution of myocardial perfusion at the time of administration. The region of hypoperfused myocardium on the initial images varied widely from 9% to 68% of the left ventricle and was significantly greater in anterior than in inferior infarcts (p less than 0.01). The region of hypoperfused myocardium on the final images varied widely from 0% to 63% of the left ventricle and was also greater in anterior infarcts (p less than 0.01). The final hypoperfused region correlated (r = -0.82) with the late resting ejection fraction and with the late regional wall motion score in the infarct segment for both anterior (r = -0.74) and inferior (r = -0.97) infarcts. There was a significant decrease (-13 +/- 11%, p less than 0.003) in the extent of hypoperfused myocardium between the initial and final studies in the patients who received thrombolytic therapy compared with an insignificant increase (4 +/- 6%, p greater than 0.5) in the patients who did not receive thrombolytic therapy. Tomographic imaging with Tc-Sestamibi permits determination of the amount of hypoperfused myocardium "at risk" in acute myocardial infarction. The change in myocardial perfusion determined by Tc-Sestamibi before and after therapy in acute myocardial infarction is a promising tool for assessing treatment.

Aged↗
PubMed1988

Use of a metal ring-marked catheter for geometric calibration in quantitative coronary angiography.

Quantitative coronary angiography depends on accurate measurement of catheter shaft diameter for correction of X-ray magnification errors. We compared the use of coronary catheters with a single metal ring (R), inserted during manufacture, with measurements using the edges of the catheter shaft (S) as a calibration mark. Both ring and shaft were 2.50 mm in diameter. On unmagnified X-ray images, the ring measured 2.49 +/- 0.40 mm, and the shaft measured 2.39 +/- .040 mm in diameter. Quantitative coronary angiography using both ring and shaft for calibration provided the same percent stenosis (R:72 +/- 12; S: 71 +/- 13), but stenosis cross-sectional area was 28% different (R: 1.44 +/- .24; S: 1.84 +/- .34 mm2). Use of the catheter shaft for calibration causes overestimation of actual coronary artery dimensions. To prevent this problem, absolute measurements of coronary artery dimensions should be made with metal ring-marked catheters.

Angiocardiography↗
PubMed1988

Antithrombotic therapy after myocardial reperfusion in acute myocardial infarction.

The problem of post-thrombolytic reocclusion can be approached in several ways. 1) Better thrombolytic agents with longer duration of effects and more powerful properties aimed at enhanced clot lysis and anticoagulation are under study. 2) The combination of high dose heparin and low dose aspirin is proposed for all patients with an acute myocardial infarction treated with thrombolytic agents. 3) Peptide inhibitors of thrombin and monoclonal antibodies against platelet glycoprotein receptors and adhesive macromolecules are potentially effective inhibitors of platelet aggregation and thrombus formation during or after thrombolytic therapy.

Coronary Disease↗
PubMed1988

Emergency thrombolysis in acute myocardial infarction.

The goal of thrombolytic treatment in acute myocardial infarction is to reestablish permanent blood flow, salvage ischemic myocardium, and reduce mortality. If patency is achieved sufficiently early and is maintained, left ventricular function is preserved and mortality decreases. The recent experience with tissue plasminogen activator and streptokinase in the TIMI I trial is reviewed with specific attention to reperfusion, reocclusion, and bleeding. Other studies concerning left ventricular preservation and mortality are also discussed. Current guidelines for antithrombotic therapy and thrombolysis are discussed. It is extremely important to adequately select patients to avoid side effects. Thorough lysis of the thrombus must be achieved to reduce the risk of rethrombosis. Simultaneous heparin should be administered to treat ongoing thrombosis. Additional antithrombotic therapy with aspirin and acute vasodilation to reduce vasoconstriction probably also decrease the likelihood of reocclusion. Because this treatment predisposes to bleeding, extreme care should be taken to avoid vascular punctures and invasive procedures in these patients. The association of immediate percutaneous transluminal coronary angioplasty has not been beneficial in preventing further events; on the contrary, adverse effects have been associated with this acute intervention.

Emergencies↗
PubMed1988

Importance of adequate heparin dosage in arterial angioplasty in a porcine model.

Acute occlusion after a successful angioplasty is a severe complication that has been reported in 2-12% of patients. Therefore, to determine whether there was a relation between the dosage of heparin and the presence of mural thrombosis, we studied in a pig model the relation between the dosage of heparin and acute platelet-thrombus deposition on the site of arterial injury. We retrospectively analyzed the effect of three heparin regimens on platelet deposition in 32 normal pigs (mean weight, 32.7 kg) that underwent bilateral carotid angioplasty and were sacrificed 90 +/- 26 minutes later. Pigs in protocol 1 (n = 7) received an intravenous bolus injection of 4,000 units heparin 10 minutes before angioplasty. Pigs in protocol 2 (n = 11) received two bolus injections of 4,000 units heparin 40 minutes apart; the angioplasty was performed immediately after the second bolus. Pigs in protocol 3 (n = 14) had an initial 4,000-unit bolus injection of heparin followed immediately by an infusion of 4,000 units/hr; angioplasty was performed 20 minutes after starting the infusion. 111In-labeled platelet deposition on deeply injured (torn into the media) arterial segments were 86.3 +/- 68, 56.2 +/- 56.9, and 37.7 +/- 37.7 X 10(6)/cm2 for protocols 1, 2, and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1988

Platelets, vasoconstriction, and nitroglycerin during arterial wall injury. A new antithrombotic role for an old drug.

Endothelial injury in vivo is associated with platelet deposition and a localized platelet-dependent vasoconstrictive response. To assess the influence of nitroglycerin on platelets and vasoconstriction, quantitative 111In-labeled platelet deposition (no platelets x 10(6)/cm2) of the injured segment and the degree of angiographic vasoconstriction (percent diameter narrowing proximal and distal to the dilated segment) produced during injury by balloon angioplasty of the common carotid arteries were studied in heparinized normal pigs that were sacrificed immediately after the procedure. In deeply injured (injury extending through the internal elastic lamina) compared with mildly injured (deendothelialization only) arteries, there was both greater platelet deposition (63.8 vs. 6.9, p = 0.04) and more vasoconstriction (30% vs. 19%, p = 0.02). In the presence of deep arterial wall injury, nitroglycerin given intravenously at a dose sufficient to lower mean arterial pressure by 9 +/- 2% significantly decreased both platelet deposition (16.2 vs. 63.8, p less than 0.008) and the vasoconstrictive response (20 vs. 30%, p less than 0.02) relative to control. However, in the presence of mild arterial wall injury, nitroglycerin decreased vasoconstriction relative to control (10% vs. 19%, p less than 0.01) without causing a significant decrease in the already low level of platelet deposition (5.6 vs. 6.9, respectively; p = NS), suggesting a direct smooth muscle relaxant effect of nitroglycerin. This is the first reported in vivo effectiveness of nitroglycerin in the reduction of platelet deposition after deep arterial injury.

Angioplasty, Balloon↗