No information is available about the effects of oral atenolol, a cardioselective beta-adrenergic blocking agent with no intrinsic sympathomimetic activity, on left ventricular function. Atenolol, 100 mg/day, was given to 12 hypertensive patients for 8 weeks, and its effects on mean arterial pressure (MAP), cardiac index (CI) and ejection indexes of myocardial performance were examined by echocardiography. Echocardiographic studies were performed before treatment, after 4 weeks of placebo, and repeated after 4 and 8 weeks of atenolol therapy. MAP fell by 14% and 21% after 4 and 8 weeks, respectively. CI fell by 22% and 20% and stroke index (SI) fell by 11% and 7%. Calculated peripheral resistance did not change significantly. Fractional shortening, ejection fraction and normalized mean rate of circumferential fiber shortening did not change. The normalized mean posterior wall velocity decreased after 4 weeks but returned to pretreatment levels after 8 weeks. The septal velocity increased after 8 weeks. End-diastolic volume index (EDVI) did not change, and there was no relationship between changes in heart rate and EDVI. The study shows that atenolol in the resting state has no effect on certain echocardiographic indexes of left ventricular (LV) function when given orally to hypertensive patients with normal LV size and function. The reduction in CI and SI were presumably secondary to a decrease in cardiac venous filling.

In a double-blind randomized study, 30 mg/kg of methylprednisolone sodium succinate (MPN) or 15 mg/kg of mannitol placebo (PL) were infused in 28 patients after acute myocardial infarction. Measurements were obtained immediately before and after for 24 hours after the initial infusion. The partial pressure of oxygen at 50% saturation of hemoglobin (P50) did not change significantly in vitro or in vivo after MPN, whereas 2,3 diphosphoglycerate (2,3 DPG) increased from 13.2 to 14.2 mumol/g Hb (p < 0.05) in the group receiving PL. The arteriovenous oxygen difference (Ca-VO2) remained constant after MPN or PL. The cardiac index (CI) increased after MPN (p < 0.02) associated with an increase in the oxygen consumption index (CI X A-V O2) from 146 to 170 ml/min/m2 (p < 0.05). These data show that MPN increases CI after acute myocardial infarction, but has no specific effects on P50, 2,3 DPG or Ca-VO2.

The Persantine-Aspirin Reinfarction Study (PARIS) was a randomized, controlled, double-blind study of dipyridamole (Persantine) and aspirin in secondary prevention of coronary heart disease. Two thousand twenty-six men and women with myocardial infarction (MI) documented by electrocardiographic findings, clinical history and cardiac enzymes were followed for a minimum of 3 years and monitored for mortality (total and cause-specific), recurrent MI and other cardiovascular events. The study had a unique structure that provides a model for large-scale industry-sponsored clinical trials. Although financed by a private pharmaceutical firm, the study was completely independent of the funding sponsor. Sixteen American and four British clinics participated in the study, along with a Coordinating Center, and ECG Reading Center, a Central Laboratory, and a Drug Distribution Center. In addition, the study included an independent Data Quality Control Center that monitored the performance of the Coordinating Center. The rationale, organization, design and baseline results are presented in this report.

Plasma lipids and lipoprotein cholesterol concentrations were determined before and at 3 months and 1 year after partial ileal surgery in 28 male survivors of first myocardial infarction (eight normolipidemic subjects and eight type II-A, two type II-B, eight type IV and two type V hyperlipoproteinemic subjects). All subjects had marked reductions in plasma total cholesterol (average 45% and 33% in the type V subjects and 37% and 31% in the other 26 subjects at 3 months and 1 year after surgeryyy). Except for the two type V subjects, all had even more marked reductions in low-density lipoprotein (LDL)-cholesterol than in the total plasma cholesterol, averaging 51% at 3 months and 49% at 1 year after surger. There were no significant changes in high-density lipoprotein (HDL)-cholesterol levels. The hypertriglyceridemic subjects had marked reductions in plasma triglycerides and very low density lipoprotein-cholesterol, whereas the normotriglyceridemic subjects (normals and II-A) had slight increases in these two measurements after surgery. Partial ileal bypass tends to normalize elevated plasma lipid and lipoprotein levels and results in a maximal lowering in LDL-cholesterol concentrations without altering the HDL-cholesterol level.

In the Persantine-Aspirin Reinfarction Study (PARIS) trial, 2026 persons who had recovered from myocardial infarction (MI) were randomized into three groups: Persantine plus aspirin (PR/A) (n = 810); aspirin alone (ASA) (n = 810); placebo (PLBO) (n = 406). The average length of follow-up study was 41 months. Results for the three specified primary end points were: total mortality 16% lower in PR/A and 18% lower in ASA compared with PLBO; coronary mortality 24% and 21% lower; incidence of nonfatal MI plus fatal coronary disease 25% and 24% lower. These differences were not satistically significant by the study criterion (Z greater than or equal to 2.6). By life-table analysis, the rates of coronary mortality and coronary incidence were about 50% lower in the PR/A group than in the PLBO group from 8-24 months, and for coronary incidence all Z values were greater than or equal to 2.6; ASA rates were about 30% lower than PLBO rates, and for coronary incidence, Z values were greater than or equal to 2.6 at two points. For these end points, from 8-20 months, PR/A rates were about 30% lower than ASA rates, but all Z values were less than 2.0 PR/A and ASA patients entering within 6 months of last MI showed the largest percentage reductions in mortality; only the difference between PR/A and PLBO groups for 3-year coronary mortality yielded a Z value of 2.6.

In a randomized trial of pulsatile vs nonpulsatile cardiopulmonary bypass for coronary artery surgery, we studied hemodynamic and hormonal responses. Anesthesia did not produce a response but, from the time of the incision, cortisol and antidiuretic hormone levels and plasma renin activity all increased. Cortisol levels continued to rise after surgery, whereas the other began to fall. Systemic vascular resistance fell dramatically during cardiopulmonary bypass but rapidly rose after bypass with a reciprocal change in cardiac index. We did not see the changes ascribed to nonpulsatile bypass by others. There ws no difference between our pulsatile and nonpulsatile cases. High-flow cardiopulmonary bypass, vasodilating inhalation anesthesia and continuation of Inderal therapy may account for our results.

Sixteen healthy men were evaluated for left ventricular performance changes and beta-blockade after therapeutic oral doses of disopyramide and propranolol administered alone and concurrently. The volunteers were randomly assigned to receive one of two drug treatment regimens that differed in the sequence and duration of administration of the drugs. Left ventricular function was assessed by echocardiographically determined ejection fraction (EF) and systolic time intervals. Beta-blockade was assessed by changes in exercise heart rate. Both disopyramide and propranolol exhibited negative inotropic activity, as evidenced by significant, although clinically inconsequential, decreases in EF and increases in the ratio of preejection period to left ventricular ejection time. The negative inotropic effects of a single 200-mg dose of disopyramide and an 80-mg dose of propranolol were comparable, while chronic disopyramide therapy (200 mg every 6 hours for 1 week) had a greater negative inotropic effect than chronic propranolol therapy (80 mg every 8 hours for 1 week). Only propranolol had beta-adrenoceptor blocking activity. When the drugs were administered concurrently, the negative inotropic effects of oral propranolol and disopyramide were neither additive nor synergistic.

The physiology, pharmacokinetics and efficacy of atenolol, a cardioselective beta-adrenergic blocking agent, were evaluated in 10 patients with stable angina pectoris in a single-blind, dose-ranging study. After a 1-month control placebo period, atenolol was administered once daily at dosages of 25, 50, 100 and 200 mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than during the placebo period. Twenty-four-hour ambulatory ECG recordings showed a decrease in mean hourly heart rate throughout the dosing period, with preservation of diurnal variation. Maximal, symptom-limited, treadmill exercise tests performed 3 hours after drug ingestion showed significantly increased exercise time and decreased double products for all doses, but especially with 100-mg and 200-mg doses. Exercise time 24 hours after drug ingestion continued to show a decrease in maximum heart rate and double product, with 100-mg and 200-mg doses again being most effective. Atenolol serum levels correlated with percent reduction in exercise heart rate and increased exercise time. Serum levels rose linearly, with an average elimination half-life of about 10 hours after chronic oral dosing. Thus, atenolol was an effective antianginal agent and suppressed resting and exercise-stressed heart rate for 24 hours after ingestion when given in a 100-mg or 200-mg dose once daily.

Ethmozin, a phenothiazine derivative, is an antiarrhythmic drug synthesized in the USSR. Preliminary data suggest that it is effective against a diversity of ectopic arrhythmias. The present study, carried out in the USSR, was designed to assess efficacy and patient tolerance of this new drug. Thirty-seven patients with chronic, persistent, frequent and symptomatic ventricular premature complexes (VPCs) were studied. VPCs were exposed by means of 24-hour ambulatory monitoring and exercise stress testing. Two drug schedules were used. Group 1, consisting of 11 patients, received 225 mg/day of ethmozin, while group 2, consisting of 26 patients, received 600 mg/day. Acute drug testing with a single large dose of ethmozin was followed by multiple dosing for a minimum of 4 days. Placebo was given in a single-blind fashion only to responders. Only two patients in group 1 had a significant reduction in VPCs as evaluated by both monitoring and exercise testing. Fourteen patients in group 2 (54%) showed striking suppression of VPCs. Mild and transiet effects were encountered in only four of the 37 patients. We conclude that ethmozin appears to be a well-tolerated, relatively effective agent for controlling VPCs.

The Belgian Heart Disease Prevention Project is a controlled, multifactorial prevention trial involving 19,390 males aged 40-59 years employed by 30 Belgian industries. These industries were paired and randomized into a control or intervention unit. In each intervention factory, the subjects from the two highest deciles of a coronary risk-score distribution curve were given individual advice twice a year. A health education campaign was also organized in each intervention factory. In the control group, 10% of randomly chosen subjects had the same baseline examination as the whole of the intervention group. After 2 years, high-risk subjects and random samples of the control and intervention group were compared regarding the coronary risk profile by means of a multiple logistic function (MLF). In the intervention high-risk group, the MLF showed a decrease of 20%, and in the control group there was an increment of 12.5% (p less than 0.001). Comparing the random samples an increment of 25% was found in the control group vs a drop of 2.26 in the intervention group (p less than 0.001). The coronary risk profile can be altered in a middle-aged male working population through mass media health education supplemented by face-to-face counseling in high-risk subjects.

The effect of timolol vs placebo on the frequency of anginal episodes, nitroglycerin consumption and exercise performance was investigated in a double-blind, randomized, crossover study in 23 patients with angina pectoris. The optimal dose of timolol (10-30 mg twice daily) for each patient was titrated by exercise studies. Compared with placebo, timolol decreased the weekly number of anginal attacks and the weekly number of nitroglycerin tablets consumed, reduced the resting heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate, decreased the heart rate, systolic and diastolic blood pressure, and product of systolic blood pressure times heart rate at the onset of angina pectoris or marked fatigue, prolonged exercise duration, and diminished electrocardiographic evidence of myocardial ischemia. Timolol is an excellent antianginal agent when prescribed twice daily, with the optimal dose titrated by exercise studies.

Medical treatment of heart disease has improved significantly in the past 30 years. The spectacular change in the natural history of rheumatic heart disease is apparent from a 1948 article that reported that 42% of children with rheumatic heart disease died of rheumatic infection or bacterial endocarditis. Antibiotics and cardiac surgery have improved the outcome from rheumatic heart disease. Cardiopulmonary resuscitation has had a major impact on the treatment of myocardial infarction and on the management of sudden death. The fundamental principle underlying the discovery of cardiopulmonary resuscitation is reviewed, and recent developments emphasizing the importance of intrathoracic pressure in the hemodynamics of cardiopulmonary resuscitation are highlighted. The important new drugs of the last 30 years include the oral diuretics, the antihypertensives and the antiarrhythmic agents. The development of the beta-blocking agents is cited as an example of the translation of basic physiological research to medical care. Finally, the role of epidemiologic techniques in the design of clinical trials to evaluate medical therapy and hence improve medical management is discussed.

Since its creation as the National Heart Institute in 1948, the National Heart, Lung, and Blood Institute (NHLBI) has led a national biomedical research program in heart, lung, blood, and blood vessel diseases, and has become increasingly involved in complex clinical trials to validate its research findings. In addition, NHLBI sponsors demonstrations and educational activities to apply proved research findings in the health care community. NHLBI's approach to these responsibilities involves acquiring new and basic information, testing and evaluating the information, and applying it to improve prevention, detection, and treatment of disease. New equipment such as the heart-lung machine and the pacemaker, better diagnostic procedures, new operative and treatment devices, new drugs, and increased use of preventive medicine have dramatically reduced mortality from heart attack, hypertension and stroke.

A controlled trial is reported on the effects of mild-to-moderate physical activity on serum lipoproteins. After two baseline examinations 100 asymptomatic middle-aged men were randomly assigned to exercise and control groups. The exercise group participated in a 4-month exercise program that consisted of 3-4 weekly sessions. The control group was advised to maintain their previous exercise habits. The success of the program was corroborated by the increase in VO2 in the training group, but not in the control group. Serum triglycerides decreased from 1.54 +/- 0.10 to 1.27 +/- 0.08 mmol/1 (p less than 0.001) and high-density lipoprotein (HDL) cholesterol increased from 1.27 +/- 0.04 to 1.41 +/- 0.04 mmol/1 (p less than 0.01) in the exercise group during the trial. No change was seen in the control group. As the concentration of apolipoprotein AI stayed constant in both groups, the ratio HDL cholesterol/apolipoprotein AI increased only in the exercise group. The level of low-density lipoprotein (LDL) cholesterol and apolipoprotein AII decreased in both groups during the trial. The alterations in serum triglycerides and HDL cholesterol in the exercise group were not dependent on weight reduction; similar changes were also seen in subjects with constant body weight during the intervention.