The association of LDL receptor activity, LDL cholesterol level, and clinical course in homozygous familial hypercholesterolemia

Patients with homozygous familial hypercholesterolemia (FH), reveal a marked heterogeneity in plasma cholesterol levels, response to diet as well as drug treatment, and clinical course. Low-density lipoprotein (LDL) receptor activities were assessed by the rate of 14C-oleate cholesteryl ester biosynthesis in fibroblasts from 13 FH homozygotes in tissue culture. The receptor activity of the individual patients was highly correlated with initial pretreatment plasma cholesterol and LDL cholesterol levels (P less than .001, r = -0.89). In addition, the LDL receptor activity was positively correlated with the age of onset of angina based on the Cox model (P less than .035, likelihood ratio = 6.71). An association was also noted between LDL receptor activity and cholesterol reduction with drugs. These data provide direct evidence for the correlation between the heterogeneity of the LDL receptor and the expression of the clinical manifestations of homozygous FH. The determination of pretreatment plasma cholesterol level and LDL receptor activity in patients with homozygous FH provide useful parameters on which to base predictions of the clinical progression of cardiovascular disease. These parameters may also influence the selection of a program for diet and drug therapy. Patients with markedly elevated plasma cholesterol levels and very low LDL receptor activity should be considered to be candidates for multiple drug therapy, and portacaval shunt, and/or periodic plasma exchanges.     

Histologic and ultrastructural features of normal human parietal pericardium

Morphologic studies of normal anterior parietal pericardium from seven patients revealed this tissue to be composed of three layers: (1) the serosa, consisting of a surface layer of mesothelial cells and a narrow submesothellal space, (2) the fibrosa, containing variously oriented layers of collagen fibrils and small elastic fibers, and (3) the epipericardial connective tissue layer, containing mainly large coarse bundles of collagen and forming part of the pericardiosternal ligament. Scanning electron microscopic examination is most useful for study of the surface features of pericardial mesothelial cells, which have single cilia and are covered with microvilli. The latter bear friction and increase the surface area for fluid transport. Junctional complexes between adjacent mesothelial cells consist of desmosomes, which reinforce intercellular adhesion and zonulae occludentes, which form permeability barriers. Actin-like filaments (50 Å in diameter) are present in microvilli and in immediately subjacent regions of the cells; these filaments mediate changes in cell shape. Intermediate filaments (100 Å in diameter) are associated with desmosomes and form bundles in the perinuclear regions; these filaments provide structural support to the cytoplasm.     

Structure and classification of cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients

Morphologic studies were made of cuspal tears and perforations in 16 porcine valve bioprostheses that had been implanted in 14 patients (9 male and 5 female) ranging in age from 2 to 65 years. Eleven bioprostheses had been in the mitral position for 30 to 123 months, four in the aortic position for 15 to 40 months and one in a valved pulmonary conduit for 96 months. The cuspal lesions were classified into four types. Type I lesions, which involved the free edges of the cusps, were the most common of all lesions and occurred with equal frequency in mitral and aortic bioprostheses. Regardless of position of implantation, type I lesions were more frequent in the right coronary cusp than in the other cusps. Ultrastructural study showed that these lesions develop as consequences of breakdown of collagen at the free edges of the cusps, usually near the commissures. Type II lesions consisted of linear perforations that extended along the basal regions of the cusps, forming an arc parallel to the sewing ring. These lesions were uncommon and resulted from separation of bundles of collagen. Type III lesions, which were large, round or oval perforations that occupied central regions of the cusps, were more common in aortic than in mitral bioprostheses. They were characterized by marked destruction of cuspal tissue and were most frequently associated with infection. Type IV lesions were small pinhole-like perforations; they usually were multiple, localized in central regions of the cusps and associated with calcific deposits. Type IV lesions were more common in mitral than in aortic bioprostheses. Regardless of position, they were more frequent in the left and noncoronary cusps than in the right coronary cusp (which may be protected by its muscle shelf against this type of perforation). It is concluded that cuspal tears and perforations develop in implanted bioprostheses as consequences of structural failure of connective tissue components.     

Calcific deposits in porcine bioprostheses: Structure and pathogenesis

Gross, histologic and ultrastructural studies were made of 14 porcine valve bioprostheses that were found to contain calcific deposits at the time of removal either at reoperation (13 patients) or at necropsy (1 patlent). Eleven bioprostheses had been in the mitral position, 1 fn the aortic, 1 in the tricuspid and 1 in a pulmonary condult. The ages of the patients at the time of implantation ranged from 2.5 to 65 years (average 32), and the bioprostheses had been in place from 3 to 94 months (average 39). Analysis of these 14 bioprostheses and review of reports concerning 37 other calcified porcine bioprostheses suggest the following conclusions: (1) Calcific deposits occur commonly in bioprostheses implanted in patients of all ages, but are more likely to become severe and clinically significant in children and in young adults than in older patients. (2) Calcific deposits can lead to prosthetic valve stenosis, because they can limit the mobility of the cusps; however, they can also be associated with prosthetic valve regurgitation. (3) Metabolic disorders that could contribute to bioprosthetic calcification are not identifiable in most patients having calcified prosthetic tissue valves. (4) The two main sites of deposition of calcium phosphate in porcine valve bioprostheses are the connective tissue in the cusps, particularly in the spongiosa, and small thrombi on the surfaces. (5) Calcification of connective tissue first involves the collagen fibrils; calcification of thrombi involves the mitochondria in platelets and leukocytes trapped in the mesh of fibrin. From these two sites, calcific deposits can grow and spread into other areas of the cusps.     

Occurrence and significance of endothelial cells in implanted porcine bioprosthetic valves

Histologic and scanning and transmission electron microscopic studies were made to determine the frequency of occurrence of endothelial cells in 49 porcine valve bioprostheses removed from 43 patients 2 days to 113 months (average 35 months) after implantation. Endothelial cells were found in none of 17 bioprostheses in place for less than 1 year, in 5 (23 percent) of 22 in place for 1 to 5 years and in 7 (70 percent) of 10 in place for longer than 5 years.The 12 bioprostheses in which endothelial cells were present had been implanted in the atrioventricular position (7 of 32 in the mitral position and 5 of 6 in the tricuspid position) for 21 to 113 months (average 71). Endothelial cells were not found in any of 11 bioprostheses implanted in the semilunar position (9 in the aortic position and 2 in pulmonary conduits); however, all but one of these bioprostheses had been in place for less than 5 years. Endothelial cells were concentrated along the basal regions of the cusps. These cells did not grow in direct contact with valve collagen, but were attached to fibrin, thrombi or fibroelastic host tissue (fibrous sheath) on the valve surfaces. The growth of endothelial cells and associated fibrous tissue may serve to increase the structural stability of bioprosthetic valve cusps, which may be of functional importance several years after implantation when the porcine connective tissue may have undergone significant deterioration.     

Exercise performance after septal myotomy and myectomy in patients with obstructive hypertrophic cardiomyopathy

The effect of left ventriculomyotomy and myectomy on exercise capacity and cardiac function in patients with obstructive hypertrophic cardiomyopathy has not previously been determined. In this study, 29 patients were evaluated during graded treadmill exercise before and after operation. Postoperatively, 27 of 29 patients reported symptomatic improvement and had greatly reduced left ventricular outflow gradient. Twenty-five of 28 patients (89 percent) attained higher exercise levels after operation, and this was accompanied by an increase in total body oxygen consumption from 16 to 21 ml/min per kg (P less than 0.005). A significant increase in cardiac index during maximal exercise also accompanied this improved exercise performance (5.0 to 5.7 liters/min per m2, P less than 0.05). The increase in maximal cardiac index was associated with greater desaturation of mixed venous blood (34 to 24 percent, P less than 0.02) in patients with preoperative angina. At a given level of mixed venous oxygen saturation (30 percent), overall mean cardiac index was higher postoperatively (4.6 to 5.2 liters/min per m2, P less than 0.05). These results suggest that, although several mechanisms probably contribute to symptomatic improvement after myotomy and myectomy, enhanced cardiac performance plays an important role in the majority of patients.     

Early degradation of collagen after acute myocardial infarction in the rat

After acute myocardial infarction (MI), proteolysis of necrotic myocardium is mediated by infiltrating inflammatory cells at the infarct margins. Collagen forms a structural fibroskeleton in healthy myocardium, and after MI this collagen may continue to provide significant tensile strength to the necrotic muscle wall. To determine whether collagen is also degraded (which might decrease infarct wall strength) and, if so, whether inflammatory cell proteases are implicated, hydroxyproline was measured from infarct zone and normal zone tissue from 24-hour infarcts produced in control rats and in rats made leukopenic (white blood cell count less than 300/mm3) by prior whole-body irradiation. Hydroxyproline was measured after precipitation of tissue homogenates with trichloroacetic acid to separate partially degraded collagen from larger collagen molecules that might retain structural importance. At 24 hours, there was significant (25%) collagen degradation in the infarct zone (p less than 0.01) in control rats but not in leukopenic rats. Tissue cell counts revealed a paucity of inflammatory cells in the infarct margins in leukopenic rats. Electron microscopic studies revealed greater preservation of collagen in the 24-hour-old infarcts of irradiated leukopenic rats compared with those of control rats. These results suggest that at 24 hours after experimental MI in the rat, there is significant collagen degradation mediated by inflammatory cell proteases.     

Atrial systole and left ventricular filling in hypertrophic cardiomyopathy: effect of verapamil

Many patients with hypertrophic cardiomyopathy (HC) have impaired left ventricular (LV) rapid diastolic filling. To quantitate the contribution of atrial systole to LV filling, we used radionuclide angiography to study 30 normal volunteers and 42 patients with HC before and after oral administration of verapamil (320 to 560 mg/day). LV time-activity curves were constructed by combined forward and reverse gating from the R wave, and the onset of atrial systole was determined by the P-R interval. The percent of LV stroke volume filled during rapid diastolic filling and atrial systole was then computed. Peak LV filling rate during rapid diastolic filling was expressed in end-diastolic volume (EDV)/second. Peak rate of rapid diastolic filling was not different in normal patients and those with HC (3.3 +/- 0.6 versus 3.3 +/- 1.1 EDV/s) and was within the normal range in 34 patients with HC (81%). However, the contribution to LV filling volume by rapid diastolic filling was diminished in patients with HC (83 +/- 7% normal, 67 +/- 17% HC, p less than 0.001) and the contribution of atrial systole was increased (16 +/- 8% normal, 31 +/- 18% HC, p less than 0.001). LV filling volume during atrial systole was above the upper normal limit of 31% in 17 patients (40%), including 13 patients with a normal peak filling rate. After verapamil, peak filling rate increased (to 4.2 +/- 1.2 EDV/s, p less than 0.001), percent LV filling during rapid diastolic filling increased (to 83 +/- 7%, p less than 0.001), and percent LV filling during atrial systole decreased (to 16 +/- 9%, p less than 0.001). Percent LV filling volume during atrial systole was abnormal after verapamil in only 3 patients (7%). Hence, although the peak rate of rapid diastolic filling may be normal in patients with HC, the contribution to LV filling by rapid diastolic filling is reduced and that of atrial systole is thereby increased. Increased rate and magnitude of rapid diastolic filling during verapamil is associated with decrease and normalization of the contribution of atrial systole to LV filling. These data suggest that many patients with HC are at risk of hemodynamic decompensation with the onset of atrial fibrillation or other tachyarrhythmias and loss of the atrial contribution to LV filling. This risk may be reduced during verapamil therapy.     

Morphologic features of the normal and abnormal mitral valve

Anatomic and functional features of the normal and abnormal mitral valve are reviewed. Of 1,010 personally studied necropsy patients with severe (functional class III or IV, New York Heart Association) cardiac dysfunction from primary valvular heart disease, 434 (43%) had mitral stenosis (MS) with or without mitral regurgitation (MR): unassociated with aortic valve stenosis or regurgitation or with tricuspid valve stenosis in 189 (44%) patients, and associated with aortic stenosis in 152 (35%), with pure (no element of stenosis) aortic regurgitation in 65 (15%) patients, and with tricuspid valve stenosis with or without aortic valve stenosis in 28 (6%) patients. The origin of MS was rheumatic in all 434 patients. Of the 1,010 necropsy patients, 165 (16%) had pure MR (papillary muscle dysfunction excluded): unassociated with aortic valve stenosis or regurgitation or with tricuspid valve stenosis in 97 (59%) patients, and associated with pure aortic regurgitation in 45 (27%) and with aortic valve stenosis in 23 (14%) patients. When associated with dysfunction of the aortic valve, pure MR was usually rheumatic in origin, but when unassociated with aortic valve dysfunction it was usually nonrheumatic in origin. Review of operatively excised mitral valves in patients with pure MR unassociated with aortic valve dysfunction disclosed mitral valve prolapse (most likely an inherent congenital defect) as the most common cause of MR. Excluding the patients with MR from coronary heart disease (papillary muscle dysfunction), mitral prolapse was the cause of MR in 60 (88%) of the other 68 patients, and a rheumatic origin was responsible in only 3 of the 68 patients, all 68 of whom were greater than 30 years of age. Mitral anular calcification in persons aged greater than 65 years is usually associated with calcific deposits in the aortic valve cusps and in the coronary arteries. Because calcium in each of these 3 sites is common in older individuals residing in the Western World, it is most reasonable to view mitral anular calcification in older individuals as a manifestation of atherosclerosis. Mitral anular calcium appears to be extremely uncommon in persons with total serum cholesterol levels less than 150 mg/dl. Mitral anular calcium may produce mild MR and, if the deposits are heavy enough, MS.     

Exercise, electrocardiographic and functional responses after percutaneous transluminal coronary angioplasty

Exercise testing after successful PTCA showed improved cardiac functional status on examination of electrocardiographic and symptomatic responses, myocardial perfusion and global and regional left ventricular function. Sixty-six patients were studied before and after persistently successful PTCA. Follow-up studies an average of 8 months after the successful procedure showed an incidence of abnormal testing of only 7% using both electrocardiographic and subjective symptomatic criteria during treadmill studies and no abnormal studies with thallium scintigraphy. Radionuclide cineangiography demonstrated similar left ventricular ejection fractions at rest before and after PTCA, but an improvement of 9 ± 10% (p < 0.001) in the exercise ejection fraction at follow-up. However, 52% of patients with paired data still had an abnormal radionuclide cineangiographic study after successful PTCA, raising the question of the presence of subclinical ischemia or a false-positive result.     

Cardiac amyloidosis causing cardiac dysfunction: Analysis of 54 necropsy patients

Clinical and morphologic findings are described in 54 necropsy patients (32 men [59%]) aged 21 to 97 years (mean 64) with cardiac amyloid deposits extensive enough to cause fatal cardiac dysfunction. Chronic congestive heart failure (CHF) was present in 46 (85%). The duration of CHF, known in 39 patients, ranged from 1 to 108 months (mean 18) and lasted ≤ 12 months in 25 patients (64%). All 8 patients without CHF died suddenly and unexpectedly. Systemic arterial pressures were recorded in the last 3 months of life in 43 patients: the peak indirect systolic pressure was ≤ 130 mm Hg and the diastolic pressure < 90 mm Hg in all. Electrocardiograms, recorded in the last 6 months of life in 40 patients, were abnormal in each: low voltage in 35 (63%); “myocardial infarction pattern” in 33 (83%); abnormal QRS axis in 29 (73%); arrhythmias in 29 (73% ); first, second, or third degree heart block in 28 (45%); and complete bundle branch block in 7 (18%). In 30 patients, the QRS amplitude in all 12 leads was measured: in the 15 men it ranged from 60 to 197 mm (mean 99) (10 mm = 1 mV) and in the 15 women from 58 to 199 mm (mean 109). Diagnosis of amyloidosis was established by biopsy of noncardiac organs or tissues during life in only 18 (33%) patients. During life the condition simulated hypertrophic cardiomyopathy in 5 patients, constrictive pericardial disease in 3, and coronary heart disease (because of angina pectoris) in 4.At necropsy, the hearts ranged in weight from 300 to 900 g (mean 554), and all but 1 had a “rubbery,” noncompliant consistency. In addition to their presence in myocardial interstitium (53 patients) and in intramural coronary arteries (54 patients), amyloid deposits were present grossly in mural endocardium in all 54 patients and in valvular endocardium in 46 (85% ). The cardiac ventricles were not dilated in 43 patients (80%), but both atria were dilated in all 54 patients. Intracardiac thrombi were present in 14 patients (26% ). Cardiac amyloidosis must be considered in any elderly patient with chronic CHF unassociated with chest pain when blood pressure is normal and the electrocardiogram discloses low voltage and a pattern of “healed myocardial infarction.”     

Amounts of coronary arterial narrowing by atherosclerotic plaques in clinically isolated,chronic, pure aortic regurgitation: Analysis of 37 necropsy patients older than 30 years

The degree of cross-sectional area (XSA) narrowing by atherosclerotic plaque in each of the 4 major epicardial coronary arteries (right, left main, left anterior descending and left circumflex) was determined at necropsy in 37 patients (30 men and 7 women) aged 34 to 77 years (mean 54) with severe, isolated, chronic, pure aortic regurgitation (AR). In 7 patients (19%), ≥ 1 major coronary artery was narrowed 76 to 100% in XSA at some point. Of the 148 major coronary arteries examined in the 37 patients, 12 arteries (8% ) were narrowed at some point 76 to 100% in XSA. Each of the 148 major coronary arteries were divided into 5-mm-long segments (average 53 per patient) and a histologic section from each segment was examined. Of the 1,977 segments, 1,087 were narrowed 0 to 25%, 669 (34%) 26 to 50%, 170 (9%) 51 to 75%, 48 (2%) 76 to 95% and 3 (0.001%) 96 to 100%. The average amount of XSA narrowing by atherosclerotic plaque per segment was about 28%. Of the 37 patients, 9 had had angina pectoris, 2 of whom had significant (> 75% XSA reduction) coronary narrowing; 2 other patients had had acute myocardial infarction clinically, 1 of whom had significant coronary narrowing at necropsy. Thus, in general, the amount of coronary narrowing in our 37 adults with severe, pure, isolated, chronic AR was relatively mild.     

The floating heart or the heart too fat to sink: Analysis of 55 necropsy patients

Certain clinical and morphologic findings are described in 55 patients whose hearts at necropsy contained so much fat that they floated in water. The patients were 47 to 89 years old (mean 67). Symptomatic coronary heart disease was present in 28 (51%) and valvular heart disease (mitral stenosis) in 3 (5%). The heart at necropsy was enlarged (>350 g for women and >400 g for men) in 45 patients (82%). The mean heart weight for the 31 women was 470 g and for the 24 men, 515 g. In addition to the severe increase in fat in the atrioventricular sulci and over both ventricles, the amount of fat in the atrial septum was increased in all patients. In 14 patients (25%), the thickness of the atrial septum cephaled to the fossa ovale was ≥2 cm. Excessive fat in this location is called “lipomatous hypertrophy of the atrial septum.” Of the 16 patients (29%) with fatal acute myocardial infarction, 7 (44%) had rupture of either the left ventricular free wall or ventricular septum. The high frequency of cardiac rupture in these patients supports the contention that rupture during acute myocardial infarction is more common in the fatty than in the non-fatty heart.     

Origin of the right coronary artery from the left sinus of Valsalva and its functional consequences: Analysis of 10 necropsy patients

Clinical and necropsy findings are described in 10 patients in whom the right coronary artery arose from the left coronary sinus and then passed to the right atrioventricular (A-V) sulcus by coursing between the aorta and the pulmonary trunk. In 7 of the 10 patients, the coronary anomaly never caused symptoms of cardiac dysfunction. In the other three, all of whom died suddenly, the coronary anomaly was the only significant abnormality found at necropsy: One patient had recurring ventricular tachycardia, one had typical angina pectoris and, in one, sudden death was the initial manifestation of cardiac dysfunction. Review of previous angiographic studies during life of 31 patients reported to have origin of the right coronary artery from the left sinus of Valsalva indicated that 9 had symptoms of cardiac dysfunction in the absence of intraluminal coronary narrowing or associated noncoronary cardiac disease. Thus, origin of the right coronary artery from the left sinus may produce cardiac dysfunction that can be fatal.     

Sudden death in prinzmetal's angina with coronary spasm documented by angiography: Analysis of three necropsy patients

Clinical and necropsy findings are described in three patients who had angina pectoris at rest, S-T segment elevation on electrocardiography during chest pain, coronary arterial spasm on angiography and sudden death. Although significant “fixed” coronary narrowing (that is, narrowing due to atherosclerotic plaques) was appreciated by angiography in only one of the three patients, necropsy disclosed in all three patients severe fixed coronary narrowings involving particularly the artery in which spasm had been demonstrated during life. Additionally, examination of each 5-mm long segment of the coronary artery that had been spastic during life (two patients) disclosed several focally spastic segments at necropsy, indicating that spasm persisted after death. Although most previously described necropsy patients with Prinzmetal's angina had some fixed coronary narrowing, underlying fixed narrowing may be difficult to identify angiographically as demonstrated by the three patients in this study.     

Coronary artery disease in the hurler syndrome: Qualitative and quantitative analysis of the extent of coronary narrowing at necropsy in six children

The amount of cross-sectional area luminal narrowing in each 5 mm segment of each of the four major epicardial coronary arteries (right, left main, left anterior descending and left circumflex) is described at necropsy in six children (aged 3 to 16 years) with the Hurler syndrome. In five patients at least one of the four major coronary arteries was narrowed 76 to 100 percent, and in four of these five patients all four major arteries were narrowed to this extent. Of the 24 major coronary arteries in the six patients, 17 (71 percent) were narrowed 76 to 100 percent at some point. A total of 182 segments were examined from the 24 major coronary arteries, and the extent of narrowing was as follows: 96 to 100 percent, 14 (8 percent); 76 to 95 percent, 61 (34 percent); 51 to 75 percent, 59 (32 percent); 26 to 50 percent, 39 (21 percent) and 0 to 25 percent, 9 (5 percent). By applying a score of 1 to 4 to each 5 mm segment according to its category of narrowing (1 = 0 to 25 percent; 2 = 26 to 50 percent; 3 = 51 to 75 percent and 4 = 76 to 100 percent), the 182 segments had a total score of 570 and a mean score of 3.2, indicating that each segment was narrowed an average of about 67 percent in cross-sectional area. Thus, narrowing of the major epicardial coronary arteries at necropsy is usually diffuse and severe in the Hurler syndrome, which is the cause of the most severe coronary narrowing in childhood.     

Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy: III. Effects of long-term administration

To determine the efficacy of long-term therapy with verapamil in patients with hypertrophic cardiomyopathy, 78 patients began treatment with the drug in the hospital. Sixty-two patients (79 percent) were in New York Heart Association functional class III or IV despite treatment with beta receptor blocking drugs. Fifty-four percent of all patients evaluated (42 of 78) and 63 percent of those discharged from the hospital (42 of 68) experienced sustained symptomatic improvement 6 to 30 months (median 14 months) after initiation of verapamil therapy. Of these 42 patients in improved condition, 25 had improvement by at least one New York Heart Association functional class, 14 improved by less than one functional class, two felt better taking verapamil than propranolol, and in one patient verapamil controlled asymptomatic ventricular tachycardia. Of the 53 patients who had the obstructive form of the disorder and were considered operative candidates, 25 (47 percent) experienced sufficient improvement so as to forgo operation. In patients remaining on verapamil therapy, the duration of treadmill exercise performed 5 days after the start of verapamil therapy increased by 3.1 ± 0.6 minutes (53 ± 10 percent, p < 0.001) from the value obtained with no medication before verapamil. A further increase of 2.3 ± 0.6 minutes (25 ± 7 percent, p < 0.0025) over the initial value with verapamil was recorded on the patients' last vistt (median 12 months after the start of therapy). Echocardiographic measurements of wall thicknesses and left atrial dimension demonstrated no significant changes during 1 year of verapamil treatment in 31 patients. Administration of verapamil was associated with adverse hemodynamic effects in 9 patients (12 percent) and adverse electrophysiologic effects In 10 (13 percent): Three patients died (with pulmonary edema) and 6 had to have treatment terminated. These results indicate an important role for long-term verapamil therapy in the treatment of hypertrophic cardiomyopathy, but patients must be carefully selected and followed up closely for the development of important adverse hemodynamic or electrophysiologic effects.     

Influence of sulfinpyrazone and naproxen on infarct size in the dog

To assess the potential role of platelet inhibitory agents in the treatment of myocardial infarction, the effect on infarct size of two platelet inhibitors, sulfinpyrazone and naproxen, was evaluated. In addition to platelet inhibition, sulfinpyrazone increases epicardial collateral flow and naproxen has lysosomal-stabilizing activity. Thirty-eight open chest dogs were given intravenously sulfinpyrazone (30 mg/kg, n = 11), naproxen (30 mg/kg, n = 14) or saline solution (n = 13) 10 minutes before and 3 and 6 hours after ligation of the mid left anterior descending coronary artery. Drug doses were sufficient to inhibit adenosine diphosphate-induced platelet aggregation. The dogs were killed 72 hours after occlusion. Myocardium at risk of infarction—that is, the area supplied by the occluded artery (anatomic risk area)—was identified by simultaneous perfusion of the aortic root with Evans blue and of the coronary artery distal to the occlusion with clear saline solution. Hearts were sliced horizontally and stained with triphenyl-tetrazolium-chloride. The infarcted area and anatomic risk area were measured with videoplanimetry. The percent of left ventricle infarcted was not significantly different among the control, sulfinpyrazone and naproxen groups (28 ± 2, 30 ± 1, 28 ± 2 percent, respectively) nor was percent of anatomic risk area infarcted significantly different (75 ± 3, 79 ± 3, 75 ± 3 percent, respectively). Thus, neither sulfinpyrazone nor naproxen in platelet inhibitory doses altered infarct size. These results indicate that neither inhibitory effects on platelet function and prostaglandin synthesis nor associated lysosomal-stabilizing properties identify agents with consistent infarct-sparing action.     

Status of the major epicardial coronary arteries 80 to 150 days after percutaneous transluminal coronary angioplasty. Analysis of 3 necropsy patients

Certain clinical and necropsy cardiac findings are described in 3 men who had percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending (LAD) coronary artery 80, 90, and 150 days before sudden death. Each patient had a decrease in the mean transstenotic coronary gradient (17, 38, and 43 mm Hg) and an angiographic increase in the LAD luminal diameter (55, 60, and 65%). At necropsy, the LAD coronary artery in the area of the PTCA in each patient was narrowed 76 to 95% in cross-sectional area by atherosclerotic plaques. No cracks in plaques or other lesions which may have resulted from the PTCA procedure were identified histologically in the LAD coronary artery of any patient.