Exercise training and reduction of some coronary risk factors in female cigarette smokers.
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Adult↗
Biomedical subjects
E A Amsterdam
Publications and source records attributed to E A Amsterdam.
Limitation of reperfusion injury by a monoclonal antibody to C5a during myocardial infarction in pigs.
The complement system has been implicated in reperfusion injury during acute myocardial infarction. We therefore attempted to reduce reperfusion injury with a monoclonal antibody (MAb) to the complement component, C5a. In 13 control pigs and 9 pigs pretreated with this MAb, ischemia was induced by a 50-min occlusion of the left anterior descending coronary artery, followed by 3 h of reperfusion. Infarct area (as percent of risk area) was reduced from 58 +/- 5% in controls to 38 +/- 7% (P < 0.05) in MAb-treated animals. Heart rate-systolic blood pressure product, left ventricular (LV) first derivative of pressure, LV end-diastolic pressure, and coronary blood flow were similar (P > 0.05) in the two groups. At 15 min of reperfusion, immunoreactive factor Bb began to increase significantly (P < 0.05) in regional coronary venous plasma, consistent with activation of the alternative complement pathway. The anti-C5a MAb did not attenuate formation of the membrane attack complex (C5b-9) as assessed by a hemolytic complement assay. Myocardial myeloperoxidase activity, a marker of tissue neutrophil concentration, was similar in the risk regions of the two groups, suggesting that neutrophil infiltration was unaltered by the MAb. However, in vitro the MAb (15 and 30 micrograms/ml) reduced C5a-stimulated neutrophil aggregation (67.4 and 70.9%), chemotaxis (52.5 and 81.4%), degranulation (66.7 and 75.8%), and superoxide generation (26.7 and 100%). In conclusion, myocardial infarction-reperfusion is associated with activation of the alternative complement pathway. Furthermore, a MAb to C5a that inhibits neutrophil cytotoxic activity, but neither the membrane attack complex nor myocardial neutrophil accumulation, decreases infarct size in pigs. These data suggest an important role of the alternative complement pathway and C5a in the propagation of ischemia cardiac damage during reperfusion.
Animals↗
The value of ten common exercise tolerance test measures in predicting coronary disease in symptomatic females.
The diagnostic contribution of ten common exercise tolerance test (ETT) measures compared with coronary angiography was studied in 62 symptomatic females (mean age = 53 +/- 9 years). Logistic regression revealed that maximal ST-segment depression, the percent of predicted maximal heart rate achieved, and test chest pain all contributed unique predictive information and formed a model generating probabilities for coronary disease (CAD). Using a predicted probability for the presence of CAD of 0.50 as a cutpoint, test accuracy was markedly improved (sensitivity = 73%, specificity = 94%, and overall correct classification rate = 90%) over the standard ST response. We conclude that multivariate analysis using these three easily assessed ETT measures provides superior discrimination between symptomatic women with and without CAD when compared to changes in the ST-segment alone.
Coronary Angiography↗
Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital for suspected acute myocardial infarction.
More than 2 million patients are admitted to U.S. hospitals annually for clinical suspicion of acute myocardial infarction (AMI), and > 70% are found not to have had a cardiac event. This study evaluates the safety and efficacy of immediate exercise testing for patients admitted to the hospital for suspected AMI. Ninety-three nonconsecutive low-risk patients admitted to the hospital from the emergency department to rule out AMI underwent exercise treadmill testing using a modified Bruce protocol immediately on admission to the hospital (median time < 1 hour). Twelve patients had positive exercise electrocardiograms, 6 of whom had significant coronary narrowing by angiography. An uncomplicated non-Q-wave AMI was diagnosed in 1 patient. Fifty-nine patients had negative and 22 patients had nondiagnostic exercise electrocardiograms. Of these 81 patients, 44 were discharged immediately after exercise testing, 17 were discharged within 24 hours, and 20 were discharged after 24 hours of observation. There were no complications from exercise testing. There were 2 late noncardiac deaths and 1 late AMI. Thus, immediate exercise testing of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission is effective in further stratifying this group into those who can be safely discharged immediately and those who require hospitalization.
Adult↗
Nonpharmacologic therapy for coronary artery atherosclerosis: results of primary and secondary prevention trials.
The association between abnormal serum lipoprotein levels and coronary atherosclerosis has been established by extensive clinical, experimental, and epidemiologic evidence. Recent angiographic trials in patients with coronary artery disease have demonstrated that improvement in serum lipids and other risk factors has a favorable effect on coronary lesions and reduces coronary events and interventions. Most trials of coronary disease prevention have used intensive pharmacologic therapy, but several have involved only nonpharmacologic intervention. The latter investigations include both primary and secondary prevention studies. Three controlled, nonpharmacologic primary prevention trials with long-term follow-up used dietary management aimed at lowering serum cholesterol levels; one trial also included smoking cessation, and one used a comprehensive approach to risk-factor modification. Serum cholesterol levels and other risk factors were significantly decreased in the intervention groups but were unaltered in the control populations. After periods of 5 to 10 years, reductions of 20% to 45% in coronary events were observed in the intervention groups compared with controls. Four secondary intervention trials examined the effect of nonpharmacologic therapy alone on coronary artery disease regression; three of these trials included control groups. All of the trials focused on reduction of elevated serum cholesterol levels with a low-fat diet, and several included interventions for other risk factors. Serum cholesterol levels fell by 14% to 24% in treated patients compared with 4% to 9% in controls. Although these trials were of relatively short duration (1 to 3 years) and included small numbers of patients (36 to 90), each demonstrated favorable effects on coronary lesions and three revealed clinical benefits.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Trials as Topic↗
Rationale for intermittent nitrate therapy.
Tolerance to the pharmacologic and therapeutic effects of nitrate therapy is now well established. This phenomenon may be defined as either a decreased response to a given amount of nitrate or the need for an increased amount of nitrate to maintain a constant effect. Tolerance has been demonstrated with all forms of nitrate therapy that maintain continuous blood levels of the drug, including frequent oral dosing, constant intravenous infusion, and continuous transdermal delivery. It can develop rapidly after only a few doses of a nitrate preparation and tends to be partial rather than absolute. Strategies for the prevention of nitrate tolerance include the avoidance of maximum nitrate doses and the use of intermittent nitrate dosing regimens. Providing a relatively brief nitrate-free interval restores vascular responsiveness to nitrates, most likely due to a recovery of the metabolic mechanisms responsible for the therapeutic effect of these drugs. The duration of this period of nitrate abstinence varies, depending on the nitrate preparation used but is generally in the range of 8-12 hours. Such intermittent therapy not only reduces the risk of nitrate tolerance, but also provides a convenient approach to outpatient management.
Drug Administration Schedule↗
Contractile actions of C5a on isolated porcine myocardium.
Although intracoronary administration of the complement component, C5a, produces deleterious effects on regional coronary blood flow and segmental ventricular function, it is unclear whether a direct myocardial action contributes to the dysfunction induced by the anaphylatoxin. We therefore evaluated the effects of purified porcine C5a on contractile tension of isolated supported ventricular trabeculae from pig hearts. Muscles were studied in a myograph bath at 30 degrees C, electrically stimulated 12 times per minute, and stretched to produce maximal isometric developed tension. C5a concentrations of 30, 100, and 300 ng/ml increased tension (P less than 0.05) 9.8, 5.5, and 20.9%, respectively. In seven of nine muscles exposed to 300 ng/ml C5a, tension initially decreased 10.5% (P less than 0.05) before the positive inotropic effect. Tachyphylaxis was demonstrated by lack of contractile response to a second administration of C5a greater than 70 min after the initial exposure to the complement fragment. Blockade of histamine H1 receptors with diphenhydramine (10(-6) M) markedly attenuated both the positive and negative contractile responses to C5a. beta-Adrenoceptor blockade with propranolol (5.6 x 10(-7) M) did not alter the response to C5a. Levels of thromboxane (Tx)B2, the stable metabolite of TxA2, were augmented in the bath after exposure to C5a (59 +/- 27.3 to 104 +/- 28.2 pg/ml, P less than 0.05). Although the TxA2 agonist, U-46619 (50 ng/ml), significantly increased tension, TxA2 receptor blockade with SQ 29548 (50 ng/ml) did not alter the response to C5a.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
A multitissue organ bath evaluated using new rabbit papillary muscle isolation methods.
A multitissue organ bath was developed to study four isolated muscle preparations simultaneously under identical conditions. The multitissue bath was evaluated by determining the dose-response curves to dobutamine in isolated rabbit right ventricular papillary muscles. Several new procedures were developed to diminish the contracture shortening that often accompanies papillary muscle excision in this species. The excised heart was dissected in a hypothermic (22 degrees C) 'relaxing solution' containing 180 mM NaCl and 5.6 mM glucose, and a 'transfer clip' maintained constant, reproducible resting tension on the isolated muscle after its excision. Rabbit papillary muscles (n = 13) isolated with these procedures and studied in the multitissue bath were stimulated at a frequency of 20/min at 30 degrees C in a modified Krebs solution containing 2.5 mM Ca2+. Mean developed tension was 3.3 +/- 0.5 g/mm2. The dose-response curve for dobutamine demonstrated a maximal increase of dT/dt, an index of contractility, at 10(-4) M (173.6 +/- 35%, p less than 0.01). The multitissue bath may be useful for simultaneous comparison of chronotropic and inotropic effects of interventions on right atrial and ventricular preparations, respectively, or for comparison of intervention effects on selected vascular strips.
Animals↗
The value of chest pain during the exercise tolerance test in predicting coronary artery disease.
UNLABELLED: The predictive power of 10 common exercise test parameters compared with coronary angiography was studied. Only the exercise electrocardiogram (EXECG), maximal rate pressure product (MAXRPP), and exercise chest pain (EXCP) contributed unique predictive information with the emergence of two interactions involving EXCP (EXCP.EXECG and EXCP.MAXRPP). IN CONCLUSION: (1) EXCP appears to be a more serious finding only in those higher risk individuals with either a positive EXECG or lower MAXRPP; (2) EXCP and its interactions may help discriminate between anginal and nonanginal, exertional chest pain, and (3) the contradictory results found when EXCP was allowed to interact may explain conflicting results in previous multivariate models regarding the predictive significance of EXCP.
Adult↗
Efficacy of cardioselective beta-adrenergic blockade with intravenously administered metoprolol in the treatment of supraventricular tachyarrhythmias.
The efficacy of intravenously administered metoprolol, a cardioselective beta-adrenergic blocking agent, was evaluated in the treatment of supraventricular tachyarrhythmias in 16 patients. The arrhythmias that were treated were atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardia (2 patients), and multifocal atrial tachycardia (1 patient). Mean dose of metoprolol was 9.5 mg (range: 2-15 mg) administered in one or two separate infusions of up to 7.5 mg each over a cumulative maximum interval of 25 minutes. In the 13 responders (81%), mean ventricular rate decreased from 134 +/- 6 to 106 +/- 7 beats/min 10 minutes after metoprolol administration and was controlled for 40 to 320 minutes without further therapy. Minimum ventricular rate (98 +/- 6 beats/min) was reached 48 minutes after initiation of metoprolol. Metoprolol reduced ventricular rate by greater than 15% (decrease of 26-60 beats/min) in 11 (69%) of 16 patients, including 9 (82%) of 11 patients with atrial fibrillation. In two other patients, one with atrial fibrillation and one with supraventricular tachycardia, ventricular rate was reduced by greater than 12%. Hypotension, occurring in five patients, was the most frequent side effect but was transient and readily managed. Cardioselective beta-adrenergic blockade by metoprolol was rapidly effective in controlling ventricular rate in a majority of patients with supraventricular tachyarrhythmias and may be of particular use in selected patients with chronic obstructive pulmonary disease in whom intravenous beta-adrenergic blockade is indicated. Hypotension is an important potential side effect.
Adult↗
Role of granulocytes and C5a in myocardial response to zymosan-activated serum.
Although previous studies have demonstrated that complement (C)5a causes myocardial ischemia and mechanical dysfunction, the cardiac response of endogenously produced C5a and C5a des-Arg in zymosan-activated serum (ZAS) and the critical role of granulocytes in this process are poorly understood. Therefore, we compared the coronary and cardiac effects of ZAS and purified C5a and investigated the role of leukocyte adhesion-promoting receptors (i.e., CD11/CD18). Like purified C5a, ZAS (0.5 ml) significantly reduced coronary artery blood flow and regional segment shortening, whereas coronary venous granulocyte concentration and myocardial lactate extraction were significantly decreased. A monoclonal antibody (MoAb) to C5a/C5a des-Arg attenuated ZAS-induced cardiac alterations. Three minutes of continuous infusion of C5a or ZAS induced sustained decreases in coronary venous granulocyte concentrations, although coronary flow and segment shortening returned to control levels after 2 min. Another MoAb, IB4, directed against CD18, significantly inhibited ZAS-induced granulocyte extraction and associated cardiac effects. Thus, cardiac dysfunction occurs after activation of the complement cascade with zymosan resulting in extraction of granulocytes mediated by the CD18 adherence glycoprotein. Furthermore, intramyocardial retention of granulocytes appears necessary for the initial and full ZAS-induced cardiac dysfunction.
Anaphylatoxins↗
Predictive value of a negative exercise electrocardiogram.
Conventionally, if an exercise electrocardiogram does not show evidence of ischemia, the patient must have achieved at least 85% of the predicted maximum heart rate for that test to be considered negative. However, no documentation of the validity of this practice exists. Thus, we evaluated the exercise electrocardiograms of 164 patients who had also undergone coronary angiography within 6 months of the exercise test. The predictive value of a negative exercise electrocardiogram was determined for each percentage point between 50 and 90% of the age-predicted maximum heart rate achieved or exceeded. The predictive value was found to increase modestly between 65 and 80% of the predicted maximum heart rate with no major changes above or below this range. Thus, it appears reasonable (in the setting of a hospital-based exercise laboratory) to either consider a negative exercise electrocardiogram as a valid finding if at least 80% of the predicted maximum heart rate is achieved, or preferably to simply report the negative finding with the percent maximum heart rate attained and the proviso that the predictive value of the test is progressively improved as higher heart rates are attained.
Adult↗
Sudden death during exercise.
Although death during exercise is rare, vigorous physical activity is associated with increased risk for fatality, particularly in individuals with overt cardiac disease or a high coronary risk profile. The mechanism of death is usually a lethal ventricular arrhythmia, but this may vary depending on the underlying cardiac condition. Cardiac disease is present in the great majority of individuals who die during exercise. In young persons, hypertrophic cardiomyopathy and congenital coronary anomalies are most frequent, whereas older victims usually have coronary artery atherosclerosis. Cardiac disease is typically unrecognized before the fatal event in young individuals; in the older group, most have overt coronary disease or identifiable risk factors. Screening asymptomatic subjects to identify increased cardiac risk during exercise is problematical in terms of logistics, expense and accuracy. However, careful evaluation, including exercise testing, is mandatory before a program of increased physical activity is initiated in cardiac patients. For other individuals, firm guidelines are lacking, and the extent of the evaluation must be determined on an individual basis.
Death, Sudden↗
Role of thromboxane A2 in the cardiovascular response to intracoronary C5a.
Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Silent myocardial ischemia: practical application of evolving concepts.
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Coronary Disease↗
Effects of high resistance training in coronary artery disease.
Resistive activities for cardiac patients have traditionally been discouraged. The purpose of this study was to assess the safety and efficacy of a 30 min/day, 3 day/week, 10-week strength training program in 9 stable, aerobically trained, male cardiac patients. The strength training program comprised lifting 80% of maximum voluntary contraction at 5 stations: quadriceps extension, bench press, standing biceps curl, hamstring curl and military press and performing 80% of the maximum number of sit-ups in 1 minute. Maximum voluntary contraction for each lift and body composition via body weight, hydrostatic weighing, skinfolds and girths were determined before and after training. The electrocardiogram was monitored during all maximum voluntary contraction lifts and heart rate and systolic and diastolic blood pressures were monitored during all activities. The only change in measures of body composition was an 11% increase in quadriceps girth (p less than 0.05). Maximum voluntary contraction increased 17, 12, 19, 53 and 46% for bench press, military press, standing biceps curl, quadriceps extension and hamstring curl, respectively (p less than 0.01), while the number of sit-ups performed in 1 minute increased 33% (p less than 0.05). No signs or symptoms of ischemia or abnormal heart rate or blood pressure responses were observed during the strength training program. Thus, resistive training at 80% of maximum voluntary contraction appears to be both safe and efficacious in stable, aerobically trained cardiac patients.
Aged↗
Effect of cardiac rehabilitation on postprandial response to a high fat meal in patients with coronary artery disease.
Past studies have shown decreased lipemic responses to a high fat meal in healthy trained vs. untrained subjects. The purpose of this study was to characterize fasting lipid profiles and lipemic responses in 13 male cardiac patients (6 in cardiac rehabilitation (CR) and 7 controls (NONCR]. Body composition and dietary composition were assessed. Plasma total cholesterol (TC), HDL-cholesterol (HDL-C) and triglyceride (TG) were determined after a 12-h fast. Subjects consumed a high fat meal (60% of calories) and the lipemic response to the meal was assessed by determining plasma TG hourly for 8 h following the meal. CR had a lower percent body fat than NONCR (26% vs. 34%, P less than 0.05). CR consumed fewer calories from fat than NONCR (28% vs. 41%, P less than 0.05). There were no significant differences between groups in TC, HDL-C or TG, although the differences approached significance (P less than 0.10). CR had a lower TC/HDL-C ratio than NONCR (5.0 vs. 7.7, P less than 0.05). Lipemic responses between groups were similar. There was no significant difference in peak TG, time to peak TG, or area under the TG curve between CR and NONCR groups. Thus, subjects undergoing cardiac rehabilitation appear to have both a more favorable diet and fasting lipid profile than NONCR; however, both groups had a similar response to a high fat meal.
Adult↗
Angiotensin-converting enzyme inhibition for congestive heart failure: achievements and potential.
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Angiotensin-Converting Enzyme Inhibitors↗