bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of ventricular ectopic depolarizations by flecainide acetate, a new antiarrhythmic agent.
Authors: Hodges M , Haugland J M , Granrud G , Conard G J , Asinger R W , Mikell F L , Krejci J
Published: June 2011

Flecainide acetate, a new antiarrhythmic agent, was given orally to 11 hospitalized patients with chronic high-frequency ventricular ectopic depolarizations. Drug effectiveness was evaluated with a dose-ranging single-blind protocol, which included placebo control and washout periods. Twice-daily dosing (average daily dose 436 mg) completely suppressed all ventricular ectopic activity in five of 11 patients; average suppression in the 11 patients was 96.3%. Complex ventricular arrhythmias, which were present in all 11 patients during the placebo control period, were completely suppressed in eight patients and markedly suppressed in the other three patients during flecainide therapy. Ejection fraction and velocity of circumferential fiber shortening measured by M-mode echocardiography did not change significantly during flecainide dosing. Ventricular arrhythmias returned in all patients during the placebo washout period. During subsequent outpatient therapy with flecainide, significant suppression was present after 1 and 2 weeks of treatment (94.4% and 93.3%, respectively). Drug elimination was slow (average plasma half-life 20 hours). Ninety-five percent suppression of ventricular ectopic depolarization during dosing and 5% reappearance of arrhythmias during washout occurred with flecainide concentrations of 200-800 ng/ml. Side effects occurred in five of 11 patients, but did not require discontinuation of the drug. These results indicate that flecainide is a very effective antiarrhythmic agent that merits further clinical investigation.
Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease.
Authors: Reeves W C , Cunningham D , Schwiter E J , Abt A , Skarlatos S , Wood M A , Whitesell L
Published: June 2011

The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.
Effect of perfusion pressure distal to a coronary stenosis on transmural myocardial blood flow.
Authors: Bache R J , Schwartz J S
Published: June 2011

We tested the hypothesis that reductions of perfusion pressure distal to a flow-limiting coronary artery stenosis can directly impair perfusion of the subendocardial myocardium. Dogs were instrumented with an electromagnetic flowmeter probe and a variable occluder on the proximal left circumflex coronary artery. Coronary perfusion pressure was measured with a catheter distal to the occluder. Coronary autoregulation was abolished by intraarterial infusion of adenosine to produce maximal coronary vasodilation. The transmural distribution of myocardial blood flow was measured with radioactive microspheres during unimpeded arterial inflow, when the occluder was progressively narrowed to reduce distal coronary pressure to approximately 70%, 50% and 35% of the control coronary perfusion pressure, and during total coronary occlusion. Heart rate, left ventricular diastolic pressure and the fraction of coronary artery flow during systole remained constant throughout the study. Progressive reductions of coronary perfusion pressure were accompanied by direct reductions of the subendocardial/subepicardial blood flow ratio (r = 0.83). Examination of the relationship between myocardial blood flow and coronary perfusion pressure showed that blood flow decreased linearly with perfusion pressure, with flow ceasing at a positive pressure (zero-flow pressure). Blood flow data from four transmural myocardial layers from epicardium to endocardium showed that this zero-flow pressure increased progressively from 10 +/- 2.1 mm Hg in the subepicardium to 18 +/- 2.3 mm Hg in the subendocardium (p less than -.01). Consequently, as coronary pressure was reduced, the zero-flow pressure represented a progressively greater fraction of coronary pressure in the subendocardium than in the subepicardium. This effect appeared to account for the progressive redistribution of blood flow away from the subendocardium that occurred as coronary pressure was decreased. Myocardial vascular resistance did not change as a result of changes in coronary perfusion pressure.
Two-dimensional echocardiographic assessment of left ventricular volumes and ejection fraction in children.
Authors: Mercier J C , DiSessa T G , Jarmakani J M , Nakanishi T , Hiraishi S , Isabel-Jones J , Friedman W F
Published: June 2011

The ability of two-dimensional echocardiography to measure left ventricular volumes and ejection fraction was evaluated in 25 children with congenital heart disease. Dimensions and planimetered areas were obtained in the short-axis view at the mitral valve and high and low papillary muscle levels and in the apical two- and four-chamber views. Eight algorithms using five geometric models were assessed. Left ventricular end-diastolic volume, end-systolic volume and ejection fraction were compared with data from biplane cineangiocardiograms. The correlation varied with the algorithm used. Algorithms using short-axis views appeared superior to those using only apical long-axis views. Four algorithms estimated left ventricular volumes with equal accuracy (Simpson's rule, assuming the ventricle to be a truncated cone; Simpson's rule, assuming the ventricle to be a truncated ellipse; hemisphere cylinder; and ellipsoid biplane). The single algorithm that best estimated left ventricular ejection fraction was the ellipsoid biplane formula using the short-axis view at the papillary muscle level (r = 0.91, slope = 0.94, SEE = 6.7%). Thus, two-dimensional echocardiography can accurately assess left ventricular volumes and ejection fraction in children with congenital heart disease.
The influence of verapamil on serum digoxin concentration.
Authors: Klein H O , Lang R , Weiss E , Di Segni E , Libhaber C , Guerrero J , Kaplinsky E
Published: June 2011

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.
Treatment of frequent ventricular arrhythmia with encainide: assessment using serial ambulatory electrocardiograms, intracardiac electrophysiologic studies, treadmill exercise tests, and radionuclide cineangiographic studies.
Authors: DiBianco R , Fletcher R D , Cohen A I , Gottdiener J S , Singh S N , Katz R J , Bates H R , Sauerbrunn B
Published: June 2011

The effects of encainide on ventricular arrhythmia and left ventricular function were studied in 21 patients with chronic, high-grade ventricular arrhythmia using a prospective, 3-month, placebo-controlled, single-blind trial design. Encainide caused a 96% decrease in the average hourly frequency of ventricular premature complexes (VPCs) and comparable reductions in salvos of nonsustained ventricular tachycardia (VT) and episodes of sustained VT. Intracardiac electrophysiologic testing showed prolonged intraatrial and intraventricular conduction times and increased atrial, atrioventricular nodal, and ventricular refractory periods with both i.v. and oral encainide without His-Purkinje block, despite marked prolongation of HV and QRS intervals. Induced repetitive ventricular beating after ventricular extrastimuli in 15 patients showed persistent repetitive ventricular beating with chronic oral encainide in seven patients, four of whom had sustained VT within 2 months of treatment on encainide. Encainide did not reduce exercise capacity or left ventricular ejection fraction at rest or during supine exercise. Minor adverse effects of encainide in 11 of 21 patients included dose-related visual disturbances, dizziness and sinus pauses (less than 3 seconds). Major adverse effects included the new appearance of sustained VT in three of 20 patients (15%). Oral encainide effectively reduces the frequency and grade of VPCs, prolongs intracardiac conduction times, and does not impair left ventricular performance. However, it is associated with frequent minor side effects and uncommon but potentially severe major side effects (sustained VT), both of which apparently have a direct relationship to the size of the dose.
Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure.
Authors: Weber K T , Kinasewitz G T , Janicki J S , Fishman A P
Published: June 2011

Muscular work requires the integration of cardiopulmonary mechanisms for gas exchange and O2 delivery. In patients with chronic cardiac failure, the response of these mechanisms may be impaired, and the pattern of O2 utilization (VO2) and gas exchange during exercise would thus provide an objective assessment of the severity of heart failure. Accordingly, rates of air flow, O2 uptake, CO2 elimination and minute ventilation were determined during progressive treadmill exercise in 62 patients with stable heart failure. Exercise cardiac output, systemic O2 extraction and lactate production were measured directly in 40 patients with heart failure of varying severity. As the severity of heart failure increased from class A to D, there was a progressive decrease in exercise capacity (from 1157 +/- 154 to 373 +/- 157 seconds) and maximum VO2 (23 +/- 3.2 to 8.4 +/- 1.5 ml/min/kg). These decreases corresponded with the reduced maximum cardiac output and stroke volume during exercise. The appearance of anaerobic metabolism (580 +/- 17 to 157 +/- 7 seconds of exercise) and the corresponding anaerobic threshold (17 +/- 0.34 to 7.1 +/- 1.5 ml/min/kg), determined noninvasively, were reproducible and correlated with the rise in mixed venous lactate concentration. No apparent untoward effects were experienced during or after the progressive exercise test. We conclude that the measurement of respiratory gas exchange and air flow during exercise is an objective, reproducible and safe noninvasive method for characterizing cardiac reserve and functional status in patients with chronic cardiac failure.
Treadmill test responses to an early exercise program after myocardial infarction: a randomized study.
Authors: Sivarajan E S , Bruce R A , Lindskog B D , Almes M J , Belanger L , Green B
Published: June 2011

The effects of an exercise program started early after myocardial infraction and the added effects of an outpatient teaching-counseling program were studied. At random, 84 patients were allocated to a control group (A), 88 patients to an exercise group (B1) and 86 patients to an exercise and teaching-counseling group (B2). The same exercise program was prescribed for patients in groups B1 and B2 and was started about 4.5 days after myocardial infarction and continued for 3 months. The outpatient teaching-counseling program consisted of eight group sessions pertaining to risk factor reduction and psychosocial adjustment to myocardial infraction. A low-level treadmill test and an exercise test were performed at 3 months and the exercise test was repeated at 6 months. The clinical, hemodynamic and electrocardiographic responses to these tests were not different among the three groups. However, by the end of 3 months, patients in group B1 and B2 reported walking greater distances than patients in group A. The incidence of morbidity and mortality was not different between the groups. No deleterious or beneficial physiologic effects of an exercise program either by itself or combined with a teaching-counseling program were demonstrated. Routine medical care and our interventions were equally effective in permitting the spontaneous hemodynamics improvements after myocardial infraction. More than 3 months after myocardial infarction, the group as a whole manifested spontaneous recovery in the form of a significant decrease in resting heart rate (p less than 0.001) and a significant increase in systolic and diastolic blood pressure at rest and with submaximal exercise (p less than 0.001). No further improvements were observed between 3 and 6 months.
Comparison of medical and surgical management of coronary artery disease: methodologic issues.
Authors: Ware J H
Published: June 2011

Coronary artery bypass surgery has been recommended for patients with a wide variety of signs, symptoms, and medical histories. Investigators have used historically controlled studies, registries and randomized clinical trials to compare the efficacy of medical and surgical management of coronary artery disease in well-defined patient groups. Historically controlled studies offer a weak basis for inference because of rapid changes in medical practice and in the prognosis for patients with coronary artery disease. Randomized trials are the ideal method for comparing therapies, but only a few trials, in highly selected patients, have been completed. Thus, registry studies provide an important part of the currently available evidence. In this paper, the strengths of randomized and registry studies are compared and the need for "meta-analyses" that integrate the evidence from both types of study is discussed. The institutional variation in surgical mortality and its implication for treatment strategy are also discussed.
Changes in grafts and coronary arteries after saphenous vein aortocoronary bypass surgery: results at repeat angiography.
Authors: Bourassa M G , Campeau L , Lespérance J , Grondin C M
Published: June 2011

We studied the patency of saphenous vein aortocoronary bypass grafts in nonconsecutive and consecutive subgroups of our first 600 patients. The patency rates were 87-93% within 1 month and 74-85% approximately 1 year after surgery. The attrition rate of grafts averaged 2.2% per year between 1 and 6 years. Early occlusion was due to thrombosis; occlusion at 1 year was caused by fibrous intimal proliferation of grafts, which also led to variable reduction in caliber and to significant (greater than 50%) segmental stenoses in 5-15% of patent grafts. The most important determinant of graft patency at 1 year was the runoff capacity of the recipient arteries, followed by the quality of the surgical techniques. Late occlusion was related to atherosclerosis that became manifest only after at least 2 years. Coronary atherosclerosis progressed in more than 50% of proximal segments of grafted arteries during the first year, but little additional deterioration occurred between 1 and 6 years. During the first year, only 10% of preexisting stenoses in nongrafted arteries showed progression of disease; progression in these vessels increased to 46% at 6 years and was no longer different, for preexisting lesions greater than 50%, from that of grafted arteries. A close correlation was observed between changes in grafts and in coronary arteries and long-term survival or relief of angina. Ninety-four percent of patients with all grafts patent and 98% with an optimal correction were alive at 6 years compared with 70% of patients without patent grafts or surgical correction. Changes in grafts or coronary arteries were observed in two-thirds of patients in whom functional deterioration occurred between 1 and 6 years, compared with 18% in whom improvement persisted after surgery.
Survival in subgroups of patients with left main coronary artery disease. Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease.
Authors: Takaro T , Peduzzi P , Detre K M , Hultgren H N , Murphy M L , van der Bel-Kahn J , Thomsen J , Meadows W R
Published: June 2011

This report presents the 42-month survival experience of 91 patients with a significant lesion of the left main coronary artery in the Veterans Administration Cooperative Study of Coronary Bypass Surgery. Survival in surgical patients was significantly better than that in the medical group (p = 0.016), even after adjustments were made for two important differences in baseline characteristics--duration of angina and high risk by angiographic criteria--between the two groups (p = 0.019). Subgroups based on severity of left main stenosis and on left ventricular (LV) function showed significant trends in favor of surgery in patients with more than 75% left main stenosis and in those with abnormal LV function. A similar but nonsignificant trend was seen in the two subgroups with 50-75% stenosis or with normal LV function. The surgical benefits were not significantly different between the categories of the subgroups defined separately by stenosis and LV function. Low-, middle- and high-risk subgroups based on four noninvasive clinical predictors also showed significantly improved survival with surgery in the high-risk group. The low-risk groups showed a slight, nonsignificant disadvantage with surgical treatment. These data support the view that patients with left main disease are not a homogeneous group. High- and low-risk subgroups with different outcomes and responses to treatment can be delineated by angiographic or clinical criteria. For most patients with left main disease, coronary artery bypass grafting offers improved longevity.
Ambulatory arrhythmias in resuscitated victims of cardiac arrest.
Authors: Weaver W D , Cobb L A , Hallstrom A P
Published: June 2011

One hundred forty-four patients with coronary heart disease previously resuscitated from out-of-hospital ventricular fibrillation underwent 24-hour ambulatory ECG monitoring 5 months (median) after cardiac arrest. Patients were then followed for an average of 31.7 months. Fifty-one patients died, 32 from subsequent unexpected cardiac arrest. One hundred twenty-nine patients (90%) had uniform ventricular ectopy. Two-thirds had complex ventricular ectopy (Bigeminy/trigeminy, repetitive forms or frequent multiforms). Complex ectopy, present in 20% or more of the 30-minute recording intervals, occurred in 18 of the patients (56%) who developed subsequent cardiac arrest, compared with 26 of 92 (28%) who survived (P less than 0.005, specificity 72%, relative risk 2.3). Other forms of ventricular ectopy, e.g., uniform, multiform and repetitive beats, were more sensitive but less specific predictors of death or recurrent ventricular fibrillation. Complex ventricular ectopy was associated with certain clinical histories: it occurred in 95% of patients with a history of congestive heart failure and in 79% with remote myocardial infarction, compared with 59% and 56% without these histories (p less than 0.001 and p less than 0.01). As expected, mortality was also greater in patients who had these clinical characteristics. Complex ectopy was related to mortality regardless of the clinical history.
Blade atrial septostomy: collaborative study.
Authors: Park S C , Neches W H , Mullins C E , Girod D A , Olley P M , Falkowski G , Garibjan V A , Mathews R A , Fricker F J , Beerman L B , Lenox C C , Zuberbuhler J R
Published: June 2011

During the past 4 years, five institutions have collaborated in evaluating the efficacy of blade atrial septostomy. The procedure was performed in 52 patients, including 31 with transposition of the great arteries, 10 with mitral atresia, five with tricuspid atresia and six with miscellaneous anomalies. The patient's ages ranged from 1 day to 12 years (mean 13 months). Improvement occurred in 41 of 52 patients (79%). Four patients had an intact interatrial septum, and blade atrial septostomy was successfully performed by a transseptal technique. One patient died from a lacerated left atrial wall; other complications occurred in four patients. Blade atrial septostomy is an effective palliative procedure, even when the interatrial septum is thickened or intact.
The pressor effect of moderate alcohol consumption in man: a search for mechanisms.
Authors: Arkwright P D , Beilin L J , Vandongen R , Rouse I A , Lalor C
Published: June 2011

Thirty pairs of drinking and nondrinking men, matched for age and weight, were drawn from a working population in which a close relationship between alcohol consumption and blood pressure had been demonstrated. In this smaller sample, men who drank an average of 408 ml of ethanol/week had higher supine (126.9 +/- 2.3 mm Hg) and standing (113.3 +/- 2.5 mm Hg) systolic and supine diastolic blood pressure (75.5 +/- 2.2 mm Hg) than nondrinkers (117.5 +/- 2.0, 107.4 +/- 2.2 and 68.9 +/- 1.8 mm Hg, respectively). Resting plasma concentrations of free and sulfated norepinephrine and epinephrine, renin activity, angiotensin II, aldosterone and cortisol were similar in drinkers and nondrinkers. To investigate differences that may arise when sympathoadrenal activity was stimulated, the subjects underwent a series of standardized physiologic stresses: isometric hand grip, mental arithmetic, cold pressor testing, standing and bicycle exercise. Blood pressure and heart rate responses were similar in drinkers and nondrinkers, although the differences in blood pressure between the two groups tended to become smaller after certain stresses. No differences in the plasma levels of free or conjugated catecholamines were apparent after these stresses. Plasma renin activity increased only after bicycle exercise, and this was similar in both groups. Plasma cortisol levels did not increase. The higher blood pressure in drinkers, therefore, cannot be explained by increased activity of the sympathoadrenal and renal pressor mechanisms.
Changes in cholesterol and triglyceride as predictors of ischemic heart disease in men.
Authors: Glynn R J , Rosner B , Silbert J E
Published: June 2011

We examined the relation of longitudinal changes in cholesterol and triglyceride to the subsequent development of heart disease. The data were from 1437 participants of the Normative Aging Study, a prospective study of men from the Boston area who were free of ischemic heart disease on two examinations approximately 5 years apart. Forty-four had symptoms or ECG findings of ischemic heart disease after their second but before their third examination, a period of 3-5 years. The risk of heart disease was studied using a multiple logistic risk model that took into account smoking and other risk factors. Changes in cholesterol and triglyceride levels between Exams 1 and 2, when corrected for regression to the mean, were better predictors of heart disease incurred between Exams 2 and 3 than initial levels of cholesterol, triglyceride or systolic blood pressure. When two age groups (28-52 years and 53-85 years) were considered, changes were important predictors in each age group. These findings suggest the importance of monitoring lipid changes over time.
The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction.
Authors: Romson J L , Hook B G , Rigot V H , Schork M A , Swanson D P , Lucchesi B R
Published: June 2011

To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 (111-In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p = 0.005). Quantification of the platelet-associated 111In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction.
Ultrasonic imaging of the coronary arteries in open-chest humans: evaluation of coronary atherosclerotic lesions during cardiac surgery.
Authors: Sahn D J , Barratt-Boyes B G , Graham K , Kerr A , Roche A , Hill D , Brandt P W , Copeland J G , Mammana R , Temkin L P , Glenn W
Published: June 2011

We explored techniques that would allow the surgeon to localize coronary artery lesions demonstrated angiographically or to supplement angiographic information in patients who are undergoing coronary artery bypass procedures by intraoperative scanning of the coronary arteries using ultrasound. A 9-MHz electronically focused water-path ultrasound scanner was first used to image the coronary arteries in three anesthetized, open-chest sheep. In a subsequent study, 10 human subjects undergoing cardiac surgery for valve replacement who had normal coronary angiograms were scanned during heart surgery to provide images of normal coronary arteries. The ultrasound probe was sterilized with gas and placed directly on the beating heart by the surgeon. In the third phase of this study, 21 patients with coronary artery disease were scanned and the ultrasonic appearance of their imaged coronary lesions was compared to independently interpreted angiographic estimates of percent obstruction, with close correlation (r = 0.91). The ultrasound scan could be used to identify lesions in vessels beyond proximal occlusions, which are not visualized well angiographically, and could localize the site of lesions to determine placement of saphenous vein bypass grafts. This new technique may provide a method for evaluating coronary atherosclerotic lesions during coronary artery surgery and aid decisions regarding placement of saphenous vein grafts.
Calcification of porcine prosthetic heart valves: a radiographic and light microscopy study.
Authors: Cipriano P R , Billingham M E , Oyer P E , Kutsche L M , Stinson E B
Published: June 2011

To determine the incidence and extent of calcification of implanted glutaraldehyde-treated porcine prosthetic heart valves, 82 valves explanted from 73 patients were examined for calcium by radiography and light microscopy. At the time of valve implantation, the patients were 2 1/4-76 years old. The included 15 children (patients younger than 15 years of age, mean age at time of valve implantation 8.7 +/- 4.1 years) and 58 adults (patients older than 15 years, mean age at time of valve implantation 53.5 +/- 15.1 years). Valves explanted from children (average time implanted 4.6 +/- 1.7 years) included four aortic, five mitral, as well as six right ventricle-pulmonary artery conduits and one left ventricle-abdominal aorta conduit. Valves explanted from adults (average time implanted 3.2 +/- 2.5 years) included 32 aortic and 32 mitral, as well as one tricuspid valve and one valve from a right ventricle-pulmonary artery conduit. Calcification of explanted valves was graded from 0 to 4+ based on radiographs. All 16 valves from children were calcified, with grade 3+ or 4+ calcification in each of the aortic and mitral valves. In adult patients, calcification was present in 10 of 33 valves (30%) implanted for less than 3 years (average time implanted 1.0 year), in nine of 11 valves (82%) implanted for 3-5 years (average time implanted 3.7 years) and in 21 of 22 valves (96%) implanted for 5 years or longer (average time implanted 6.2 years). Analysis of variance demonstrated that calcification was strongly related to the duration that valves were implanted (p less than 0.001). Age at the time of valve implantation also had a strong effect (p less than 0.001) on the amount of valvular calcium. Valves from children showed the most calcification, and the amount did not change when valves were implanted in patients 30 years of age or older. Patient sex and valve position had no effect on the amount of calcification. Calcification occurred at each right- and left-heart valve position, most frequently at sites of commissural attachments.
The cellular electrophysiologic mechanism of the dual actions of disopyramide on rabbit sinus node function.
Authors: Katoh T , Karagueuzian H S , Jordan J , Mandel W J
Published: June 2011

To determine the contribution of disopyramide's suggested opposing direct depressant and indirect acceleratory actions on sinus node function, we studied the effects of disopyramide, 1 x 10(-7) to 1 x 10(-4) M, on isolated rabbit sinus node preparations using standard microelectrode techniques. Transmembrane potentials were recorded simultaneously from the sinus node and adjoining crista terminalis area. Disopyramide, as much as 1 x 10(-5) M, had no effects on the sinus cycle length. At a concentration of 1 x 10(-4) M, sinus cycle length was significantly prolonged due to prolongation of the sinus nodal action potential duration. During cholinergic blockade with atropine, 1 x 10(-6) M, disopyramide, 1 x 10(-7) to 1 x 10(-4) M, significantly prolonged sinus cycle length as a result of a prolongation of the sinus nodal action potential duration and a decrease of the slope of phase 4 depolarization. During cholinergic stimulation with carbamyl choline, 1 x 10(-9) M, disopyramide, 1 x 10(-7) to 1 x 10(-6) M, tended to reverse carbamyl choline-induced prolongation of the sinus cycle length (NS). This acceleratory action of disopyramide was caused by a significant increase of the slope of phase 4 depolarization. Disopyramide, 1 x 10(-7) to 1 x 10(-4) M, had no significant effects on corrected sinus node recovery time or on sinoatrial conduction time under any conditions studied. We conclude that disopyramide has a direct depressant action on normal sinus node cells at the upper therapeutic and toxic levels, which is enhanced during cholinergic blockade, and that disopyramide's acceleratory action appears only at much lower concentrations and only during cholinergic stimulation.
Pirbuterol, an oral beta-adrenergic receptor agonist, in the treatment of chronic cardiac failure.
Authors: Weber K T , Andrews V , Janicki J S , Likoff M , Reichek N
Published: June 2011

Pirbuterol (PB), an oral beta-adrenergic-receptor agonist, has the pharmacologic effects of vasodilation and positive inotropy. The present studies were undertaken to determine the value of PB in the long-term therapy of chronic cardiac failure. A double-blind, randomized, 7-week trial comparing PB (20 mg three times daily) with placebo in 12 patients was followed by 12 weeks of open PB therapy. Dose-dependent nervousness and tremulousness limited the unit PB dose to less than 20 mg in six patients. In all patients, clinical status, exercise tolerance and maximal oxygen uptake, left ventricular echocardiographic dimension and cardiothoracic ratio were unchanged from control after 7 weeks of placebo or PB or after 12--19 weeks of PB. To assess the adequacy of 20 mg of PB, the dose-response relations of cardiocirculatory effects to 10, 15, 20 and 30 mg of PB were compared in seven of the above patients and nine other patients. Cardiac output was significantly elevated and wedge pressure reduced after all four doses, but these changes were sustained from 6 hours after 20- and 30-mg doses only. Thus, the role of PB in the management of chronic cardiac failure appears limited; judgment of its utility must await the results of additional controlled trials.
The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function.
Authors: Levin R I , Weksler B B , Jaffe E A
Published: June 2011

Sodium nitroprusside (NP) is a potent vasodilator that also inhibits platelet aggregation. To test the hypothesis that NP causes both of these effects by altering the balance between prostacyclin (PGI2) produced by endothelial cells and thromboxane A2 (TXA2) produced by platelets, we incubated each of these cell types with NP for 5 minutes and assayed the PGI2 and TXA2 produced. NP at pharmacologically achieved doses (0.01--30 micrograms/ml) inhibited platelet aggregation and resultant TXA2 synthesis in a dose- and time-dependent manner (p less than 0.001). The inhibition was not dependent on cAMP production, external calcium concentration, or suppression of TXA2 synthesis. NP did not alter the production of PGI2 by cultured human endothelial cells as measured by radioimmunoassay for 6-Keto-PGF1 alpha, the stable hydrolysis product of PGI2. However, supernates of NP-treated endothelial cells containing low, noninhibitory concentrations of NP unexpectedly inhibited platelet aggregation. This inhibition of platelet aggregation was due to synergy between PGI2 (0.1--3 nM) and NP (p interaction less than 0.03). The synergistic inhibition by NP and PGI2 of platelet aggregation and TXA2 synthesis in vivo may explain some of the beneficial actions of NP in the treatment of hypertension and congestive heart failure.
Total cholesterol and lipoproteins in school children: prediction of coronary heart disease in adult relatives.
Authors: Moll P P , Sing C F , Weidman W H , Gordon H , Ellefson R D , Hodgson P A , Kottke B A
Published: June 2011

The distribution of risk factors and the prevalence of coronary heart disease (CHD) were studied in 850 first- and second-degree relatives of 98 healthy index cases selected from 3666 school children surveyed for lipid levels in Rochester, Minnesota. Three groups of families were based on an index child's total plasma cholesterol level: 18 families with a child in less than the fifth percentile (low-cholesterol group), 47 with a child in the fifth to ninety-fifth percentiles (middle-cholesterol group) and 33 with a child in greater than the ninety-fifth percentile (high-cholesterol group). The children's cholesterol levels clustered with those of their relatives; mortality due to CHD before age 65 was increased by 2.5 times in grandfathers of index cases in the high-cholesterol group compared with those of the middle-cholesterol group (p less than 0.016). The prevalence of CHD in all the grandfathers was associated with an index child's total cholesterol, more strongly associated with an index child's low-density lipoprotein cholesterol level and most strongly associated with an index child's high-density lipoprotein cholesterol level as a fraction of total cholesterol. This study establishes that childhood lipid and lipoprotein levels from a single cross-sectional survey identify families at elevated risk for CHD.
Captopril in primary pulmonary hypertension.
Authors: Leier C V , Bambach D , Nelson S , Hermiller J B , Huss P , Magorien R D , Unverferth D V
Published: June 2011

Seven women with primary pulmonary hypertension underwent hemodynamic evaluation, at rest and during exercise, before and after the oral administration of captopril. Dose-response curves were generated for the 25-, 50- and 100-mg doses. Captopril significantly reduced systemic blood pressure and systemic vascular resistance; these effects persisted at submaximal levels of exercise. Captopril did not alter pulmonary artery pressure or resistance, cardiac output or stroke volume at rest or during exercise. Exercise tolerance did not improve. Four of the patients also received captopril chronically for 12 weeks at doses of 75 and 100 mg every 8 hours. Resting and exercise hemodynamic evaluation was repeated at the end of the 12-week period. Except for a persistent reduction in mean systemic blood pressure at rest, chronic captopril administration did not elicit hemodynamic changes. Measured exercise duration did not change during continuous captopril treatment, although one patient reported mild subjective improvement in activity tolerance. In primary pulmonary hypertension, captopril exerts its major effect on systemic vasculature, with little or no effect on the pulmonary circuit. While an occasional patient may experience some clinical improvement with captopril therapy, the majority of adult patients with severe primary pulmonary hypertension will not benefit from its chronic administration.
Termination of ventricular tachycardia by single extrastimulation during the ventricular effective refractory period.
Authors: Ruffy R , Friday K J , Southworth W F
Published: June 2011

Termination of ventricular tachycardia by low-energy shocks delivered during the ventricular refractory period has been reported. We describe a case of reproducible termination of multiple episodes of sustained ventricular tachycardia by a low-current extrastimulus delivered during the effective refractory period of the right ventricle, from the distal bipole of a quadripolar electrode catheter.
Transient collateral augmentation during coronary arterial spasm associated with ST-segment depression.
Authors: Tada M , Yamagishi M , Kodama K , Kuzuya T , Nanto S , Inoue M , Abe H
Published: June 2011

To examine the possible existence of collateral circulation during coronary artery spasm, we attempted to visualize the transient appearance of collateral vessels that could serve to salvage otherwise jeopardized ischemic areas. In three patients with vasospastic angina, total spastic obstruction of a major coronary artery was associated with transient collateral augmentation, which was supplied by the nonspastic artery during anginal period associated with ST-segment depression. These collateral vessels disappeared when the angina and ST changes resolved after nitroglycerin administration. These findings suggest that the collateral blood supply could transiently occur through preexisting vessels to perfuse the ischemic area during coronary artery spasm and that such collateral flow could have a role in preventing transmural myocardial ischemia, resulting in a lesser degree of ischemia associated with ST-segment depression.
Summary estimates of cholesterol used to predict coronary heart disease.
Authors: Castelli W P , Abbott R D , McNamara P M
Published: June 2011

The relationships of total cholesterol and the proportion of cholesterol in individual lipoprotein classes to coronary heart disease are complex. To help simplify these relationships, cholesterol values are often combined into one summary estimate to form a single risk factor with a relationship to disease that is more easily described. Although summary estimates result in convenient expressions relating cholesterols to coronary heart disease, there is the potential for sacrificing information by ignoring the joint configuration of cholesterols that make up these estimates. We investigated the extent of this possibility for the ratio of total cholesterol to high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol. The findings suggest that the summary estimates are useful expressions for combining cholesterol information and are strong predictors of coronary heart disease. Clinicians who choose to use a summary estimate for screening purposes should recognize that a single ratio estimate is not always as informative as the joint configuration of the cholesterols that make up the estimate. This possibility is most clearly exhibited for the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and it may become more apparent in future studies as the capabilities of exploring lipoprotein cholesterol relationships improve.
Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia.
Authors: Marshall R C , Tillisch J H , Phelps M E , Huang S C , Carson R , Henze E , Schelbert H R
Published: June 2011

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.
Effects of propranolol on reflex vascular responses to orthostatic stress in humans. Role of ventricular baroreceptors.
Authors: Ferguson D W , Thames M D , Mark A L
Published: June 2011

To evaluate the role of ventricular baroreceptors in humans, we studied the effects of propranolol on reflex vasoconstrictor responses to simulated orthostatic stress. We measured forearm vascular resistance in 10 normal males in the control state and during lower body negative pressure (LBNP) at -10 and -40 mm Hg before and after propranolol (0.1 mg/kg i.v.). Baseline forearm vascular resistance showed no significant change: 23.9 +/- 3.4 U (+/- SEM) before vs 28.0 +/- 0.5 U after propranolol. Reflex increases in forearm vascular resistance during LBNP at -10 and -40 mm Hg were 5.2 +/- 1.2 and 21.2 +/- 6.6 U before and 3.4 +/- 1.2 and 10.6 +/- 2.2 U, respectively, after propranolol. Thus, propranolol significantly (p less than 0.05) reduced responses to LBNP at -40 mm Hg. In contrast to the effects with LBNP, propranolol did not attenuate increases in forearm vascular resistance during the cold pressor test and handgrip, thus excluding a nonspecific depression of reflexes. We also studied the effects of propranolol on carotid baroreflex-mediated vasoconstrictor responses to neck pressure at 15 and 30 mm Hg. Propranolol had no significant effect on the vasoconstrictor responses to neck pressure. In conclusion, propranolol selectively attenuates vasoconstrictor responses to LBNP. We suggest that this results from a propranolol-induced decrease in the activity of cardiac ventricular baroreceptors. The results support the view that ventricular baroreceptors play an important role in reflex adjustments to orthostatic stress in humans.
Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure.
Authors: Leier C V , Huss P , Magorien R D , Unverferth D V
Published: June 2011

We studied 30 patients with moderate-to-severe congestive heart failure in a double-blind, randomized, placebo-controlled trial to determine the acute and long-term effects of isosorbide dinitrate on clinical status and on resting and exercise hemodynamics. Seventeen patients received placebo and 13 isosorbide dinitrate. First-dose isosorbide dinitrate (40 mg orally) decreased resting and exercise pulmonary capillary wedge pressure, pulmonic and systemic arterial pressures and pulmonic and systemic vascular resistances without augmenting exercise capacity. Compared with placebo, chronic therapy with isosorbide dinitrate (40 mg orally every 6 hours for 12 weeks) significantly improved clinical status and exercise capacity. Resting and exercise systemic blood pressure and systemic vascular resistance returned to baseline values during chronic isosorbide dinitrate therapy, but pulmonary capillary wedge pressure, pulmonary artery pressure and pulmonary vascular resistance remained improved. In patients with congestive heart failure, 12 weeks of oral isosorbide dinitrate therapy improves resting and exercise hemodynamics, exercise capacity, and clinical status; tolerance develops to the systemic arterial vascular effects without attenuation of the venous and pulmonary vascular effects.