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Biomedical subjects

P F Cohn

Publications and source records attributed to P F Cohn.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of metoprolol on early infarct expansion after acute myocardial infarction.

The effects of metoprolol on early infarct expansion after acute myocardial infarction were studied in rats (n = 54) that underwent either left coronary artery ligation (MI) or sham operation. Immediately after surgery, the rats received either metoprolol (M) by mouth, which had been dissolved in drinking water, for 72 hours supplemented with three intraperitoneal doses over the first 24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure and analyzed morphometrically. Infarct size was nonsignificantly lower in the metoprolol-treated group compared with the untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p < 0.001), lower left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O, p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm Hg/sec MI-H2O, p < 0.001), but left ventricular end-diastolic pressure and cardiac index did not differ between the two groups. Left ventricular weight corrected for body weight was higher in infarcted rats treated with metoprolol compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09 gm/kg MI-H2O, p < 0.05). The initial slope of the pressure-volume relationship Ki, an index of operative volume stiffness, was lower in infarcted rats treated with metoprolol compared with infarcted untreated rats (p = 0.03). There were, however, no significant differences in the expansion index, thinning ratio, or left ventricular volume between the two infarcted groups. Thus metoprolol therapy begun in the immediate postinfarction period promotes an increase in left ventricular weight and reduces operative volume stiffness but has no significant effect on indexes of early infarct expansion.

Animals↗
PubMed1994

Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST)

BACKGROUND: Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome, but treatment of patients with asymptomatic ischemia remains controversial. Accordingly, the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia. METHODS AND RESULTS: A multicenter, randomized, double-blind, placebo-controlled study of asymptomatic or minimally symptomatic outpatients with daily life silent ischemia due to coronary artery disease was conducted. The primary outcome measure was event-free survival at 1 year by Kaplan-Meier analysis. Events were death, resuscitated ventricular tachycardia/fibrillation, myocardial infarction, hospitalization for unstable angina, aggravation of angina, or revascularization. The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks. Three hundred six outpatients with mild or no angina (Canadian Cardiovascular Society class I or II), abnormal exercise tests, and ischemia on ambulatory monitoring were randomized to receive either atenolol (100 mg/d) or placebo. After 4 weeks of treatment, the number (mean +/- SD, 3.6 +/- 4.2 versus 1.7 +/- 4.6 episodes, P < .001) and average duration (30 +/- 3.3 versus 16.4 +/- 6.7 minutes, P < .001) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients (4.4 +/- 4.6 to 3.1 +/- 6.0 episodes and 36.6 +/- 4.1 to 30 +/- 5.5 minutes). Event-free survival improved in atenolol-treated patients (P < .0066), who had an increased time to onset of first adverse event (120 versus 79 days) and fewer total first events compared with placebo (relative risk, 0.44; 95% confidence intervals, 0.26 to 0.75; P = .001). There was a nonsignificant trend for fewer serious events (death, resuscitation from ventricular tachycardia/fibrillation, nonfatal myocardial infarction, or hospitalization for unstable angina) in atenolol-treated patients (relative risk, 0.55; 95% confidence intervals, 0.22 to 1.33; P = .175). The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks. Side effects were mild and generally similar comparing atenolol- and placebo-treated patients, although bradycardia was more frequent with atenolol. CONCLUSIONS: Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.

Activities of Daily Living↗
PubMed1993

Initial clinical presentation of cardiac disease in asymptomatic men with silent myocardial ischemia and angiographically documented coronary artery disease (the Oslo Ischemia Study).

Data concerning the natural history of asymptomatic coronary artery disease (CAD) has been limited to epidemiologic rather than angiographic studies, thus leading to uncertainty as to whether warning symptoms and signs will identify subjects with silent myocardial ischemia before morbid events. To address this issue, 50 apparently healthy men with angiographically proven CAD and asymptomatic exercise-induced ST depression have been followed prospectively for 15 years in the Oslo Ischemia Study. Fourteen men died. The initial presenting clinical event in these 14 men was chest pain in 4 (30%)--but in only 1 case was it recognized as typical angina--silent myocardial infarction in 5 (35%) and sudden death in 5 (35%). Thirty-six men survived, with 19 developing symptoms. Overall, chest pain was the first clinical event in 22 of the total of 33 men with symptoms (66%), whereas myocardial infarction occurred in 6 (18%) and sudden death in 5 (16%). Although chest pain occurred in 22 men, it was clinically diagnosed as typical angina pectoris in only 6. These observations suggest that there is an absence of clear-cut ischemic symptoms in many asymptomatic patients before morbid events.

Adult↗
PubMed1993

The effects of chronic oral milrinone therapy on early postinfarction left ventricular remodeling.

Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 +/- 0.08 mg/kg/day) dissolved in drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 +/- 0.07 ml/kg vs 2.16 +/- 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 +/- 0.03 vs 0.91 +/- 0.06, p < 0.001), and a lower expansion index (1.61 +/- 0.12 vs 2.61 +/- 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Silent myocardial ischemia.

The documentation of abnormalities related to myocardial ischemia, whether symptomatic or silent, is of central importance. Whenever this information is available, it should be used in the overall assessment of the patient at risk for adverse outcome. The level of concern for treatment of CAD should be based on the risk implications associated with the ischemia-related abnormalities detected during objective testing rather than on the presence or absence of pain. The exercise stress test is still the single most useful test to begin the evaluation of a patient with an analyzable ST segment. In persons suspected of having CAD, the detection of ischemic-type ST-segment depression, at a low workload (e.g., < 120 beats/min or < 6.5 METS) of > 2 mm magnitude or persisting for more than 6 min implies high risk for adverse outcome. Asymptomatic ischemia during everyday activities, detected by Holter monitoring, in the high-risk patient, most probably adds additional risk beyond the risk of an abnormal stress test alone. Left ventricular imaging by two-dimensional echocardiography, RNA, angiogram, vest, etc, showing an ejection fraction > or = 40%, reversible wall motion abnormalities in multiple regions and redistribution defects or a failure to increase ejection fraction during exercise even if the patient remains asymptomatic, also imply high risk. The presence of any of these abnormal findings, regardless of symptoms, should therefore prompt as high a degree of concern as with ischemia-related signals associated with pain. Thus any therapy chosen should be directed toward elimination of transient ischemia, not just relief of symptoms that may or may not be ischemia related. If this course is chosen, the efficacy of the therapeutic regimen and possible progression of CAD should be assessed with follow-up testing for ischemia. We believe that risk factor modification and aspirin should be considered for most, if not all, patients in whom ischemia, silent or symptomatic, is suspected or detected. If symptoms or ischemia suggesting low risk is present, anti-ischemic medical therapy may be considered, but follow-up is advised. If a high-risk ischemic signal, even without symptoms, is detected, medical therapy should be used to attempt to modify the signal. If the ischemic signal suggesting high risk persists despite medical therapy, revascularization should be considered. Until additional data from large clinical trials are available, this approach appears to have the greatest likelihood of modifying the adverse outcome of CAD.

Angina Pectoris↗
PubMed1992

Mechanisms of myocardial ischemia.

Traditionally, myocardial ischemia has been viewed as an imbalance in the supply and demand of myocardial oxygen. Stable angina is usually considered to involve a fixed lesion, whereas unstable angina involves a fixed lesion as well as such components as platelet aggregation, thrombotic processes, and vasospasm. Variant angina involves primarily vasospasm. A newer concept holds that most angina results from mixed mechanisms in which both fixed lesions and vasomotor alterations play a role. These mechanisms are responsible for mixed ischemic events, characterized by episodes at varying levels of exertion, with or without anginal pain. This concept would seem to be supported by the occurrence of silent ischemia in the setting of stable, unstable, or variant angina, despite differing pathophysiologic conditions. Ischemic events have important prognostic significance; unfortunately, many are unrecognized by patients. The question whether the treatment of ischemic events will improve prognosis remains a matter of debate.

Coronary Circulation↗
PubMed1992

Efficacy of enhanced external counterpulsation in the treatment of angina pectoris.

Eighteen patients with chronic angina despite surgical and medical therapy were treated with an improved system of enhanced external counterpulsation (EECP) (1 hour daily for a total of 36 hours). Patients underwent a baseline treadmill thallium-201 stress test. After EECP treatment, a thallium stress test was repeated for the same exercise duration. One week after treatment, patients also underwent a maximal stress test. All patients improved in anginal symptoms and generally decreased antianginal medications, with 16 obtaining complete relief from angina. Pre- and post-thallium stress testing performed for the same duration showed complete resolution of ischemic defects in 12 patients (67%), reduction in the area of ischemia in 2 (11%), and no change in 4 (22%). Thus, a decrease in myocardial ischemia was observed in 14 patients (78%; p less than 0.01). The exercise duration of maximal stress testing after EECP significantly improved from 8.14 +/- 0.71 to 9.72 +/- 0.77 minutes (p less than 0.005), although the double product did not change significantly. Analysis of these 2 tests in the subgroup of 14 patients with improvement in thallium studies showed significant increases in both exercise duration (8.58 +/- 0.66 to 10.44 +/- 0.59 minutes; p less than 0.001) and double product (21,827 +/- 2,044 to 24,842 +/- 1,707 mm Hg.beats/min; p less than 0.01). The improvement in reperfusion defects and increase in exercise duration are reflections of improved perfusion to ischemic regions of the myocardium. EECP uses additional thigh balloons and sequenced balloon inflation, effecting a significant increase in diastolic augmentation over previously available methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1992

Myocardial dysfunction in silent myocardial ischemia as demonstrated by ambulatory radionuclide left ventricular function studies.

Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring, monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone.

Coronary Disease↗
PubMed1991

The prognostic and economic implications of a strategy to detect and treat asymptomatic ischemia: the Atenolol Silent Ischemia Trial (ASIST) protocol.

Although silent ischemia may be linked to increases in cardiovascular morbidity and mortality, the long-term effects of a strategy aimed at the detection and treatment of this asymptomatic condition have not been fully explored. We therefore have developed the Atenolol Silent Ischemia Trial (ASIST), the first multicenter, randomized, prospective study of the prognostic implications of silent ischemia in asymptomatic and minimally symptomatic patients with coronary artery disease. Inclusion criteria for study patients were documented coronary artery disease, evidenced angiographically or by previous myocardial infarction, and transient ischemia, evidenced by abnormalities of regional wall motion, stress thallium-201, or exercise electrocardiogram. The main objective of ASIST is to assess the influence of frequency and duration of symptomatic and asymptomatic ischemic episodes on the occurrence of fatal and nonfatal cardiac events. Atenolol, a beta 1-selective adrenergic blocker, was chosen as the therapeutic intervention because of its potential benefits in treating both symptomatic and asymptomatic ischemia. Ambulatory electrocardiographic monitoring will be used to measure the frequency and duration of ischemic episodes during daily life. The predictive ability of short-term (4-week) effects on long-term (52-week) response to atenolol treatment is also being assessed, along with the economic impact of this diagnostic and therapeutic strategy. Given the current emphasis on reducing morbidity and mortality associated with coronary artery disease, ASIST results should shed light onto the long-term management and prognostic implications of this otherwise asymptomatic condition.

Atenolol↗
PubMed1991

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

BACKGROUND: Experimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. METHODS AND RESULTS: From 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. CONCLUSIONS: The present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men.

Adenosine Diphosphate↗
PubMed1990

Silent myocardial ischemia--classification and management.

As many as 10% of middle-aged men in the United States may have asymptomatic but active coronary artery disease. Additional patients have silent disease after a myocardial infarction or a combination of silent ischemia and angina. Silent and painful episodes have similar hemodynamic and electrical properties, and antianginal medications appear to have global anti-ischemic effects.

Angina Pectoris↗
PubMed1990

Effects of calcium channel blockers on the coronary circulation.

Calcium channel blockers are among the most effective antiischemic therapies currently available. These agents afford a reduction in vascular smooth muscle tone by interrupting the excitation-contraction coupling process dependent on calcium transport. The efficacy of calcium channel blockers in patients with myocardial ischemia is probably due in large part to their effects on coronary circulation. In experimental models of coronary occlusion, these agents have been demonstrated to increase coronary vasodilation and coronary blood flow. Recruitment of coronary vasodilator reserve by nifedipine has been demonstrated indirectly via enhancement of left ventricular function in a canine model. Additionally, calcium channel blockers have been shown to modify the reactive hyperemic response usually seen after coronary artery occlusion. These changes in coronary resistance vessels, which normally regulate myocardial blood flow in response to metabolic requirements, have important clinical implications. Larger collateral vessels are also affected by calcium channel blockers, although the results observed in experimental models are not as clear cut. Although techniques for measuring coronary blood flow in humans are more limited, considerable data have accumulated on the effects of calcium channel blockers in humans. Assessments of coronary vasodilation using quantitative angiography have produced variable results. However, improved myocardial perfusion, as measured by thallium-201 scintigraphy after administration of nifedipine, and beneficial effects on coronary blood flow and coronary vascular resistance as assessed using the precordial xenon-133 washout technique before and after sublingual administration of nifedipine have been observed. Overall, such studies have not only shown the clinical usefulness of calcium channel blockers, but have broadened our understanding about the complex interplay of their mechanisms of action.

Animals↗
PubMed1990

Should silent ischemia be treated in asymptomatic individuals?

In the United States, there may be as many as two million totally asymptomatic men with silent myocardial ischemia due to coronary artery disease. Because detection of such patients is often fortuitous, a rigorous screening protocol has been suggested for high-risk subgroups (i.e., persons with multiple coronary risk factors and/or family histories of premature coronary artery disease). At present, the initial procedure of choice for a screening protocol is the exercise test, followed by radionuclide procedures to differentiate true-positive from false-positive responses if coronary angiography is being considered. Holter monitoring is useful in documenting out-of-hospital ischemic events in asymptomatic patients with documented coronary artery disease. Prognostic studies in patients with and without coronary angiographic data indicate that asymptomatic patients with an ischemic ST-segment depression on exercise tests comprise a high-risk subgroup that has a well-defined morbidity and mortality due to future cardiac events. The angiographic surveys show that the greatest risk is in those individuals with more extensive disease. Treatment in asymptomatic persons requires the use of objective measurements as end points. Several reports have demonstrated the efficacy of beta-blockers, calcium channel blockers, and coronary angioplasty in this population, at least so far as reducing total ischemic activity is concerned. How nonsurgical therapy will affect ultimate prognosis is still unclear. However, surgical therapy in asymptomatic patients with left main coronary artery disease and triple-vessel disease has been reported to improve long-term survival.

Angiography↗