Coronary artery bypass grafting. A model for the understanding of the progression of atherosclerotic disease and the role of pharmacological intervention.
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Animals↗
Biomedical subjects
V Fuster
Publications and source records attributed to V Fuster.
Tetralogy of Fallot: historical lessons.
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Adolescent↗
Aortocoronary artery vein-graft disease: experimental and clinical approach for the understanding of the role of platelets and platelet inhibitors.
On the basis of our recent experimental studies in dogs and pigs and a prospective clinical study in 407 patients, we describe four consecutive phases of aortocoronary artery bypass vein-graft disease. We focus on the role of platelets in its pathogenesis and of platelet inhibitor drugs in its prevention: (1) an early postoperative phase of platelet thrombotic occlusion, which is significantly prevented by platelet inhibitor therapy when started in the perioperative period; (2) an intermediate phase of platelet-related intimal hyperplasia, within the first postoperative year, which is not prevented with platelet inhibitor therapy; (3) a late phase of occlusion, towards 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 the thrombotic type of occlusion; (4) a phase of atherosclerotic disease, after the first postoperative year, in which the role of platelets and of platelet inhibitor therapy is under investigation. Vein graft disease and occlusion rates vary widely according to time after operation and risk factors of occlusion. Currently, it appears that occlusion rates are decreasing, perhaps related to better surgical and technical experience.
Animals↗
Improved intraoperative evaluation of mitral valve operations utilizing two-dimensional contrast echocardiography.
Whenever possible, precise mitral valve repair is preferable to valve replacement. Present methods for intraoperative detection of mitral regurgitation, primarily hemodynamic measurements and direct palpation, may underestimate or not detect the presence and severity of regurgitation. We have investigated two-dimensional contrast echocardiography as a means of improving our intraoperative assessment of mitral valve function both before and after repair or replacement. After exposure of the heart, a baseline two-dimensional echocardiogram (in modified long- and short-axis planes) is performed using a hand-held 5 mHz mechanical transducer. Five milliliters of agitated 5% dextrose in water is injected into the left ventricle through a transseptal needle to generate detectable microbubbles. In the absence of mitral regurgitation, virtually all microbubbles exit through the aorta; in the presence of regurgitation, a mass of microbubbles reflux into the left atrium. After repair of the mitral valve and immediately after bypass, the contrast echocardiogram is repeated and hemodynamic measurements are obtained. Forty-three patients (37 with mitral valve disease and six additional patients without mitral disease) undergoing cardiac operations were evaluated. Experience with intraoperative two-dimensional contrast echocardiography has accurately demonstrated relatively small degrees of mitral regurgitation when conventional techniques failed to do so and has allowed more precise repair of the residual regurgitation. Two commissurotomy and two annuloplasty patients who were thought to have satisfactory repairs underwent immediate second procedures because of significant residual mitral regurgitation demonstrated solely by this echocardiographic microbubble technique. No complications associated with this technique have developed. We conclude that intraoperative two-dimensional contrast echocardiography is a sensitive and safe technique that allows intraoperative detection of even small degrees of mitral regurgitation and provides a basis for precise repair of mitral valve lesions.
Adult↗
Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy.
Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.
Adolescent↗
Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations.
To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.
Adult↗
Trial of platelet-inhibiting drug in scleroderma. Double-blind study with dipyridamole and aspirin.
In a randomized, double-blind, controlled study, 28 patients with early scleroderma received dipyridamole (225 mg/day) and aspirin (975 mg/day) or placebo for 1-2 years. No significant clinical or objective laboratory improvement was noted in either group. Platelet survival time, plasma renin activity, and coagulation tests were not predictive of disease course. Biomechanical and vascular tests of the hands correlated with clinical extent of skin induration and presence of finger ulcers, respectively.
Aspirin↗
Long-term antiarrhythmic therapy. Problem of low drug levels and patient noncompliance.
Maintenance of adequate serum blood levels is crucial to successful antiarrhythmic therapy. Serum levels of four antiarrhythmic agents (long-acting procainamide, quinidine sulfate, quinidine gluconate, and disopyramide) were determined in 98 consecutive ambulatory patients receiving long-term oral therapy. Medication dosages, dosing intervals, and time elapsed from last dosage until blood sampling were determined. Seventy-five patients (76.5 percent) had subtherapeutic blood levels (with mean levels less than 50 percent of the suggested minimum), and only 22 patients (22.5 percent) had therapeutic levels. Even among the 61 patients who claimed to have taken their medications within the six hours prior to blood sampling, 43 (70 percent) had subtherapeutic levels. These ratios held among all subgroups studied. Physicians should be aware of the high proportion of patients receiving long-term oral antiarrhythmic therapy with inadequate serum blood levels when planning therapeutic regimens.
Adult↗
Intraoperative contrast echocardiography to evaluate mitral valve operations.
Intraoperative two-dimensional contrast echocardiography was performed on 29 patients undergoing open heart surgery to determine the presence of mitral regurgitation before and immediately after the operative procedure: 14 patients had predominant mitral stenosis, 9 had severe mitral regurgitation and 6 had no mitral valve disease (control subjects). Two-dimensional echocardiography was performed by applying a 5 MHz transducer directly on the heart during injection of saline solution through an apical ventricular sump or transseptal needle, generating contrast microbubbles, with imaging in two planes. Baseline studies were performed after thoracotomy and pericardiotomy before cardiopulmonary bypass, and a second study was done after the operative procedure, with the patient off cardiopulmonary bypass with hemodynamic stabilization before chest closure. No control subject had contrast evidence of mitral regurgitation before or after cardiopulmonary bypass. Two of three patients with mitral valvuloplasty and two of five with commissurotomy required a second operative procedure before chest closure because of persistent mitral regurgitation detected by intraoperative two-dimensional contrast echocardiography. Thirteen of the 15 patients with valve replacement had no mitral regurgitation after cardiopulmonary bypass. Intraoperative two-dimensional echocardiographic findings correlated with data from postoperative clinical examinations and two-dimensional echocardiography-Doppler studies. It is concluded that two-dimensional echocardiography with contrast is an important intraoperative tool for assessing the presence and relative severity of mitral regurgitation after mitral commissurotomy, valvuloplasty or valve replacement. This technique may allow surgeons to be more aggressive in combining reparative operative procedures (that is, commissurotomy and valvuloplasty) in an attempt to retain native valves.
Adult↗
Aortic and mitral valve incompetence: long-term follow-up (10 to 19 years) of patients treated with the Starr-Edwards prosthesis.
The long-term course (mean 15 years) of 336 patients with valvular incompetence who underwent Starr-Edwards ball valve implantation between 1962 and 1971 was reviewed. Eighteen patients (10%) with aortic valve replacement and 24 (16%) with mitral valve replacement died early postoperatively. Mortality remained high (31%) in the first 3 years after aortic valve replacement; it was highest (13%) in the first year after mitral valve replacement and then approached the normal rate. The most common mode of death was sudden death after aortic and cardiac failure after mitral valve replacement. At follow-up, 76% of survivors had improved symptomatically. Three instances of primary valve malfunction occurred. The probability of freedom from thromboembolism at 15 years postoperatively was 56% for aortic valve replacement and 52% for mitral valve replacement. The Starr-Edwards valve prosthesis is durable over prolonged follow-up period, but thromboembolism remains a persistent problem. Survival may be normal for patients surviving the early postoperative years.
Adolescent↗
What do we gain from the analysis of right ventricular function?
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Echocardiography↗
Reproductive history in women with coronary heart disease. A case-control study.
Reproductive history events may be risk factors for coronary heart disease among women under age 60. In this study, the cases were 169 women under age 60 with a diagnosis of coronary heart disease while residents of Rochester, Minnesota. The first manifestation of coronary heart disease was angina in 95, myocardial infarction in 59, and sudden unexpected death in 15 women. Two age- and sex-matched controls for each case were selected from all registrations for care at the Mayo Clinic in the same year the case was diagnosed. The cases had more of the accepted coronary heart disease risk factors--i.e., hypertension (relative risk = 2.9), smoking (relative risk = 2.4), elevated serum cholesterol (relative risk = 2.6), and diabetes (relative risk = 4.1)--than did controls. In addition, women undergoing artificial menopause and those whose first pregnancy was before age 25 appeared to be at higher risk of coronary heart disease. Use of multivariate analysis to control for known coronary heart disease risk factors resulted in a relative risk of 1.9 for women whose age at first pregnancy was less than 20, and 1.8 for those whose age at first pregnancy was 20-24, as compared with those never pregnant and those whose age at first pregnancy was greater than or equal to 25.
Adult↗
Quantification of platelet retention in aortocoronary femoral vein bypass graft in dogs treated with dipyridamole and aspirin.
Autologous femoral vein segments were implanted as aortocoronary bypass grafts in 50 dogs, 25 of which were treated with dipyridamole and aspirin to inhibit platelet deposition and 25 that were not. Autologous platelets labeled with indium-111 were injected into some dogs 48 hr before they were killed on the first day after surgery; other dogs were injected 24 hr before they were killed (3, 7, 30, and 90 days after surgery). Radioactivity on the grafts and on control specimens of contralateral femoral veins was converted to quantification of platelets adhering to the vessel wall (platelets/cm2). The treated group had fewer graft platelets per square centimeter than the untreated group on postoperative days 3, 7 (p less than .01), and 30 (p less than .05). Graft and control vein platelets per square centimeter were nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy revealed deendothelialization at 1 and 7 days after grafting and reendothelialization at 30 and 90 days. The data suggest that indefinite prolongation of therapy to inhibit platelet deposition after bypass grafting may be unnecessary (although other atherosclerotic vessels may benefit from therapy).
Animals↗
Primary pulmonary hypertension: natural history and the importance of thrombosis.
A long-term retrospective follow-up study was made of 120 patients (33 male, 87 female patients) with primary pulmonary hypertension--diagnosed by strict clinical and hemodynamic criteria--to obtain a better understanding of the natural history and possible pathogenetic mechanisms of the disease. The mean age at diagnosis was 34 (3 to 64) years, but only 24 patients (21%) remained alive 5 years later. Lung tissue obtained at autopsy from 56 patients revealed two major pathologic types: thromboembolic pulmonary hypertension in 32 patients (57%) and plexogenic pulmonary arteriopathy in 18 (32%). Thus, in more than half the patients undergoing autopsy the major histologic feature was thrombi without any evidence of plexiform lesions. The two groups were similar with respect to their clinical and hemodynamic features and short survival. Of the variables tested for prognostic importance by stepwise multivariate analysis, only two were significant: pulmonary arterial oxygen saturation (p less than .00001) and anticoagulant therapy (p = .01). Anticoagulant therapy is recommended for patients with primary pulmonary hypertension.
Adolescent↗
The role of pharmacotherapy in secondary prevention of myocardial infarction and death.
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Actuarial Analysis↗
New "ex vivo" radioisotopic method of quantitation of platelet deposition - studies in four animal species.
We have developed a sensitive and quantitative method of "ex vivo" evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion.
Animals↗
Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole.
Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.
Aspirin↗
In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin.
Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.
Adult↗