Determinants of arrhythmic death during coronary artery reperfusion: Effect of perfusion bed size

To further our understanding of the factors determining the consequences of transient episodes of ischemia, we studied the influence of the size of the ischemic bed on the incidence of ventricular fibrillation (VF). The circumflex coronary artery (CFX) was occluded at various locations in 19 dogs. After 20 minutes of occlusion followed by 10 minutes of reperfusion the dogs were killed. The portion of the left ventricle (LV) at risk of infarcting ($\text{R}\text{LV}$) was defined as the region supplied by the occluded CFX and determined by simultaneous perfusion of the CFX with saline solution, just beyond the occlusion site, and of the aorta with Evan's blue. Bread loaf slices of the heart were photographed and projected, and the normal (blue) and risk regions (unstained) traced. The product of area and slice weight yielded mass of normal and risk regions. The $\text{R}\text{LV}$ of dogs that died of reperfusion VF (n = 6) was 42.3 ± 5.0%, larger (p < 0.001) than $\text{R}\text{LV}$ in all surviving dogs (n = 13), 24.2 ± 9.4%. Twelve of the 13 survivors had $\text{R}\text{LV}\text{< 35\%}$, whereas all dogs that died had $\text{R}\text{LV}\text{> 35\%}$ (p = 0.0005). As is true for VF occurring during coronary artery occlusion, the incidence of reperfusion VF is related to the size of the ischemic insult.     

The effects of nitroglycerin-methoxamine combination on infarct size in conscious dogs

The effect of nitroglycerin combined with methoxamine in reducing infarct weight was studied in conscious dogs. Ten minutes after permanent left anterior descending (LAD) coronary artery occlusion, 10 dogs received nitroglycerin (450 micrograms bolus IV, then 300 micrograms/min for 4 hours) and methoxamine as needed to maintain blood pressure and heart rate. No dogs in heart failure. Ten control dogs received saline solution. Dogs were sacrificed 3 days later. The region at risk of infarction was delineated by simultaneously perfusing the aortic root with Evans blue and the distal LAD artery with saline solution under equal pressures. Slices of stained hearts were incubated with tetrazolium to identify infarct. Total weight of left ventricle (LV), risk region, and infarct was measured. Nitroglycerin-treated dogs showed no difference from control dogs in infarct weight (26.2 +/- 5.9 gm +/- SE vs 27.7 +/- 5.6 gm), percent risk region/LV (36.0 +/- 1.4% vs 37.9 +/- 3.1%), or present infarct/LV (23.5 +/- 5.2% vs 24.8 +/- 4.9%). In a subgroup with risk region/LV less than or equal to 35%, nitroglycerin reduced infarct weight by 45% (8.8 +/- 8.5% vs 15.9 +/- 7.9%), percent infarct/LV by 49% (7.1 +/- 6.8% vs 13.8 +/- 6.6%), and percent infarct/risk region by 41% (23.0 +/- 22.0% vs 38.9 +/- 15.9%). Because of the small number of dogs in the study, differences were not significant. In dogs with risk region/LV greater than 35%, nitroglycerin had no effect. Thus, in dogs without overt heart failure, nitroglycerin may salvage ischemic tissue within small areas at risk of infarction, but the results are not definitive. However, our results clearly demonstrate that in the absence of failure, nitroglycerin does not reduce the size of large infarcts.     

Mitral valve “anular” calcium forming a complete circle or “O” configuration: Clinical and necropsy observations

Attention is called to the occurrence of a complete circle or “O”-shaped ring of calcium at the mitral anular region in each of two women, aged 67 and 82 years. Extension of mitral anular calcium from behind the posterior mitral leaflet across the ventricular aspect of the anterior mitral leaflet to form a complete circle has not been reported previously.     

Extravasated erythrocytes, iron, and fibrin in atherosclerotic plaques of coronary arteries in fatal coronary heart disease and their relation to luminal thrombus: frequency and significance in 57 necropsy patients and in 2958 five mm segments of 224 major epicardial coronary arteries

The presence of extravasated erythrocytes (EE), iron (I), and fibrin (F) within coronary atherosclerotic plaques and their relation to intraluminal coronary thrombus was determined in 2958 five-mm segments of 224 major epicardial coronary arteries in 57 patients with fatal coronary heart disease and in 1290 five-mm segments of 103 coronary arteries in 27 control (c) subjects. Intraplaque EE were present in 10% of the segments (controls [c] = 1%), in 35% of the arteries (c = 5%), and in 84% of the patients (c = 19%); I was present in 4% of the segments (c = less than 1%), in 14% of the arteries (c = 4%), and in 57% of the patients (c = 22%); intraplaque F was present in 2% of the segments (c = less than 1%), in 17% of the arteries (c = 3%), and in 63% of the patients (c = 7%). Intraluminal thrombus, present only in the patients with acute myocardial infarction and in none of the controls, occurred in 3% of the segments, in 8% of the arteries and in 26% of the patients. Intraplaque hemorrhage or EE occurred usually in the absence of intraluminal thrombus and conversely intraluminal thrombus occurred more frequently without than with underlying plaque hemorrhage. The frequency of intraplaque EE, I, and F was proportional to the amount of coronary atherosclerotic plaque present. Intraplaque I and F infrequently were observed in the absence of EE. The significance of extravasated erythrocytes, iron, and fibrin in atherosclerotic plaques remains unclear.     

Frequency and direction of interatrial shunting in valvular pulmonic stenosis with intact ventricular septum and without left ventricular inflow or outflow obstruction: An analysis of 127 patients treated by valvulotomy

This report summarizes observations in 127 patients who underwent pulmonic valvulotomy for valvular pulmonic stenosis with intact ventricular septum and without obstruction to left ventricular inflow or outflow. Of the 127 patients, 30 (24%) preoperatively by dye dilution curves had shunting at the atrial level: in 19 (63%), the shunt was right-to-left, and in the other 11 (27%), entirely left-to-right. The patients with right-to-left interatrial shunts had severe pulmonic valve stenosis (average peak systolic pressure gradient = 120 ± 11 mm. Hg) and small (average diameter 1.1 ± 0.1 cm.) sized defects in the atrial septum (patent foramen ovale). In contrast, the patients with left-to-right shunts had mild to moderate pulmonic valve stenosis (average peak systolic pressure gradient = 60 ± 5 mm. Hg) and relatively large (average diameter = 2.8 ± 0.1 cm.) defects in the atrial septum (true atrial septal defect). The patients with right-to-left interatrial shunts had no significant differences in right versus left atrial pressures. The patients with left-to-right interatrial shunts, however, had left atrial pressures significantly greater than right atrial pressures (7 ± 0.5 vs 5 ± 0.5, p < 0.05). No significant differences were found in ventricular end-diastolic pressures.     

Quantification of amounts of coronary arterial narrowing in patients with types II and IV hyperlipoproteinemia and in those with known normal lipoprotein patterns

The amount of cross-sectional area narrowing by atherosclerotic plaques in each 5 mm long segment of the left main, left anterior descending, left circumflex, and right coronary arteries was analyzed at necropsy in 15 patients with type II hyperlipoproteinemia (HLP), in 13 with type IV HLP, and in 10 with known normal lipoprotein patterns. All 38 study patients had clinical evidence of coronary heart disease. Of the 2593 five mm segments examined histologically, narrowing of 76% to 100% in cross-sectional area by atherosclerotic plaques was as follows: type II = 39%, type IV = 67%, and normal lipoprotein pattern = 35% (controls = 4%). Utilizing a scoring system of 1 to 4 for the four categories of narrowing (0% to 25%, 26% to 50%, 51% to 75%, 76% to 100%), the mean score per 5 mm segment for the patients with type IV HLP was significantly higher (3.5) than that for the patients with type II HLP (3.0), normal lipoprotein patterns (3.0), and the controls (2.3). Thus, our patients with type II HLP and those with normal lipoprotein patterns had similar amounts of severe coronary narrowing and significantly less severe coronary narrowing than the patients with type IV HLP.     

Impaired adrenal reserve in the Watanabe Heritable Hyperlipidemic rabbit: implications for LDL-receptor function in steroidogenesis

The cholesterol required for steroidogenesis may be provided by the novo biosynthesis or through the delivery of cholesterol by the circulating lipoproteins. By studying adrenocortical function, structure and biosynthetic capacity in an animal model devoid of the classical, high-affinity low density lipoprotein (LDL) receptor pathway, the respective roles of de novo cholesterolgenesis and lipoprotein cholesterol delivery were investigated. The Watanabe Heritable Hyperlipemic (WHHL) rabbit lacks the LDL-receptor pathway. The activity of the rate-limiting enzyme in cholesterolgenesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was 4- to 15-fold greater than normal in the WHHL adrenal gland. The basal corticosterone concentrations were normal in the WHHL rabbit; however, the corticosterone concentration increased by less than 50% of normal after an intravenous ACTH injection. Electron-microscopic evaluation of adrenocortical cells from the WHHL rabbits disclosed significantly increased mitochondrial surface area and diminished amounts of cytosolic lipid and lysosomal area. These data indicate that the mammalian adrenal gland utilizes endogenously synthesized cholesterol as well as cholesterol delivered through the LDL-receptor pathway. Moreover, in the absence of the LDL-receptor pathway, endogenously produced cholesterol is sufficient for normal basal glucocorticoid function.     

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.     

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.     

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.     

Strategy for evaluation and surgical treatment of the asymptomatic or mildly symptomatic patient with coronary artery disease.

Although there is no debate concerning the role of operation in severely symptomatic patients with coronary artery disease, uncertainty concerning the indications for coronary bypass operation in the asymptomatic or mildly symptomatic patient abounds. Preliminary results of the Veterans Administration Collaborative Study indicate that operation enhances survival only in patients with left main coronary artery disease. The debate this study engendered led to analyses questioning the validity of its conclusions. By utilization of nonrandomized data, it was argued that operation also increases survival in patients with significant narrowing of two or three coronary vessels. The survival data of the nonsurgically treated groups in such studies derived mainly from natural history data of populations studied 5 to 10 years ago and containing large numbers of severely symptomatic patients: The annual mortality rate in such populations has averaged about 7 and 11 percent in patients with two and three vessel disease, respectively. However, recent studies indicate that survival of asymptomatic or midly symptomatic patients with two or three vessel disease is considerably better: These patients have an average annual mortality rate of only about 2 percent. Thus, when survival data of surgically treated patients are compared with survival data of asymptomatic or mildly symptomatic patients not treated surgically, serious questions arise as to the wisdom of prophylactic operation in patients without left main coronary artery disease.Because a compelling argument can be made for operating on all symptomatic patients with left main coronary artery disease it might be justified to perform coronary angtography in all symptomatic patients with coronary disease to rule out the possibility of significant left main arterial narrowing. Alternatively, etectrocardiographic exercise stress testing may offer a reasonable alternative to determine which mildly symptomatic patients should undergo coronary angiography for detection of this disease. However, the profound economic implications of such screening studies must be considered before broad application of large scale screening is advocated.     

Ebstein's anomaly of the tricuspid valve and prolapse of the mitral valve

The hearts from 10 necropsy patients with Ebstein's anomaly of the tricuspid valve were examined for abnormalities of the mitral valve. Five patients were under 1 year of age and none had an abnormal mitral valve. The other five patients were ages 18 to 72 years (mean 36 years); all had focal fibrous thickening of the mitral leaflets and three had prolapse of one or both mitral leaflets. Only one of the three patients with mitral valve prolapse had an atrial septal defect (secundum type), indicating that the association of mitral valve prolapse with Ebstein's anomaly is not due to the presence of an atrial septal defect.     

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.