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Biomedical subjects

H Boudoulas

Publications and source records attributed to H Boudoulas.

At least 145 records · Page 8Linked to original sources

Effect of propranolol on postexercise left ventricular ejection time index.

The net delta left ventricular ejection time index 4 minutes after exercise is prolonged in many patients with coronary artery disease. This prolongation is thought to be due to the lack of response of the ischemic myocardium to adrenergic stimulation and has been proposed as a measure of myocardial ischemia. In this study, the effect of beta adrenergic blockade on net delta left ventricular ejection time was studied in nine normal subjects (Group A) and in eight patients with stable angina and coronary artery disease (Group B). In Group A, a treadmill exercise test was performed for 10 minutes before and after administration of propranolol, 160 mg daily, for 2 days. The postexercise net delta left ventricular ejection time was significantly greater after propranolol (mean +/- standard error of the mean 12 +/- 4 versus 35 +/- 4 ms, p less than 0.01). In group B a maximal treadmill exercise test was performed before and after therapy with propranolol. Only patients with a normal net delta left ventricular ejection time before propranolol were selected. The net delta left ventricular ejection time again increased significantly after propranolol (11.5 +/- 4 versus 35.3 +/- 5 ms p less than 0.01). It is concluded that prolongation of postexercise net delta left ventricular ejection time cannot be used to diagnose ischemia in patients who are receiving propranolol therapy. Our data support the hypothesis that prolongation of net delta left ventricular ejection time after exercise is caused by an impaired myocardial response to catecholamines, whether due to ischemia or effective beta adrenergic blockade.

Adult↗

Effect of increased adrenergic activity on the relationship between electrical and mechanical systole.

The effect of catecholamines and atrial pacing on the relationship between electrical systole (QT) and mechanical systole (QS2) was studied in 12 normal subjects and in 32 patients. The studied subjects were divided into three groups. Group 1 included 12 normal subjects in whom serial isoproterenol infusions were performed before and after oral propranolol administration, 160 mg daily for 2 days. During the 24-hour control period, the QT was always shorter than the QS2 (from 14 +/- 3 to 19 +/- 4 msec, p less than 0.01), while during isoproterenol infusion the QT was always greater than the QS2 (from 28 +/- 5 to 34 +/- 5 msec, p less than 0.01). Group 2 included 26 patients in whom 24-hour urinary epinephrine (E) and norepinephrine (NE) were measured the same day as systolic time interval measurements. The E + NE was higher in patients in whom the QT was longer than the QS2 compared with patients in whom the QT was the same or shorter than QS2 (107 +/- 9 vs 61 +/- 7 microgram/24 hours, p less than 0.05). Group 3 included six patients in whom the heart rate was increased with atrial pacing, from 80 to 130 beats/min. The QT was always shorter than the QS2 (from 13 +/- 3 to 24 +/- 5 msec, p less than 0.01). Adrenergic stimulation results in a relative prolongation of the QT with the QS2 shortening and the QT remaining unaffected. The QT is normally shorter than the QS2, so the duration of QT should always be considered in relationship to the duration of QS2. Finally, a reversal of the normal QT-Qs2 relationship may provide a simple index of increased adrenergic activity.

Adolescent↗

Linear relationship between electrical systole, mechanical systole, and heart rate.

The relationship between the duration of electrical systole (QT) and heart rate (HR) and the relationship between the QT interval and total electromechanical systole (QS2) were studied in the resting state in 200 patients (100 males and 100 females) without evidence of cardiovascular disease. A linear relationship was found between the QT and HR in males and females (males, QT = 521 msec - 2.0 HR, r = .91; females, QT = 511 msec - 1.8 HR, r = .90). In 20 male and 20 female subjects, the relationship between QT and QS2 was studied. The QT was slightly shorter but paralleled the QS2 (males QT = 529 msec - 2.1 HR, QS2 = 541 msec - 2.2 HR; females QT = 511 msec - 1.9 HR, QS2 = 540 msec - 2.0 HR). Thus, over the physiologic range of resting HR, a linear relationship exists between QT and HR. The QT interval is slightly shorter but parallels the QS2 in patients without heart disease. These linear relationships permit a direct comparison of the duration of electrical and mechanical systole.

Adult↗

Concentration-dependence of disopyramide binding to plasma protein and its influence on kinetics and dynamics.

Disopyramide binds to two independent sites on protein in human plasma. The first binding site located on alpha-1-acid glycoprotein has an association and a capacity constant of 1.0 x 10(6) M-1 and 3.5 x 10(-6) M, respectively, and accounts for the majority of disopyramide binding. The second site is probably located on albumin and accounts for 5 to 10% of the binding. The bound fraction of disopyramide was concentration-dependent at drug concentrations reported to be therapeutic. After administration of 100, 150, 200 and 300 mg doses of disopyramide (Norpace) to each of four human volunteers, the area under the free (unbound) disopyramide serum-concentration time curve averaged 2.32, 3.33, 5.21 and 8.24 mg/l. hr, respectively, and was directly proportional to dose. The elimination half-lives based on free and total drug concentrations averaged 4.36 and 6.51 hr, respectively (P less than .001), and were dose-independent. The peak response (change in pre-ejection period) and area under the response time curves were better related to free than to total serum concentrations of disopyramide.

Binding Sites↗

Positive inotropic effects of hydralazine in human subjects: comparison with prazosin in the setting of congestive heart failure.

Hydralazine possesses positive inotropic properties in animal model preparations. To determine whether this vasodilator elicits a positive inotropic response in the failing human ventricle, hydralazine, 75 or 100 mg, was administered orally to 14 patients with left ventricular dysfunction and congestive heart failure; the results were compared with those of first-dose prazosin at 5 and 10 mg. The duration of the preejection period and the isovolumic developed pressure/duration of isovolumic contraction (delta P/delta t) were used as indexes of inotropy. Prazosin did not effect a significant response in the duration of the preejection period or in the delta P/delta t. Hydralazine significantly shortened the preejection period and increased the delta P/delta t over 8 hours after administration; these data suggest that hydralazine elicits a positive inotropic response in the failing human ventricle.

Dose-Response Relationship, Drug↗

Effect of procainamide on left ventricular performance in patients with primary myocardial disease.

The effect of procainamide (P) on left ventricular function as measured by the systolic time intervals (STI) was studied in 14 patients with primary myocardial disease. P, 7.5 mg/kg body weight, was given intravenously at a rate of 100 mg per minute. Administration of P produced a decrease in left ventricular performance as manifest by a significant prolongation of the pre-ejection period corrected for heart rate (PEPI) and an increase of the PEP to the left ventricular ejection time (LVET) ratio. The peak effect on PEPI and PEP/LVET occurred at 2 minutes after P administration (delta PEPI + 14 +/- 1.9 ms, p < 0.001, delta PEP/LVET + 0.052 +/- 0.007, p < 0.001) with values returning towards baseline by 60 min. In 6 of the patients P blood levels were measured simultaneously with the STI measurements. Changes in PEPI and PEP/LVET directly parallel changes of P blood levels. It is concluded that P given intravenously at the usual therapeutic doses decreases left ventricular performance in patients with primary myocardial disease. These changes in left ventricular performance directly parallel procainamide blood levels.

Adult↗

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

Symptomatic patients with mitral valve prolapse (MVP) frequently mimic thyrotoxicosis, hyperadrenergic states or hypoglycemia. Twenty symptomatic patients with auscultatory and echocardiographic MVP were studied in the clinical research unit. T3, T4 and plasma cortisol were normal. Patients with MVP had normal responses to oral glucose administration but higher glucose levels than the controls (p less than 0.05). Twenty-four-hour urinary epinephrine (E) and norepinephrine (NE) were greater than normal (E + NE excretion, 44 +/- 2 vs 29.5 microgram/g creatinine, p less than 0.001). The short electromechanical systole corrected for heart rate (529 +/- 3.9 vs normal 548 +/- 2 msec, p less than 0.01) also reflected high adrenergic tone. Frequent premature ventricular complexes (PVCs) with couplets and triplets were found in 14 patients. Catecholamine excretion and frequency of PVCs were parallel and both decreased significantly at night (p less than 0.001). Plasma catecholamine increase with exercise was greater in patients in whom the number of PVCs increased more than 10 per minute compared with patients in whom the number of PVCs remained relatively unchanged (620 +/- 80 vs 98 +/- 20 msec, p less than 0.01). We conclude that symptomatic patients with MVP have high adrenergic tone that may be responsible for or contribute to the multiple symptoms.

Adolescent↗

Corticosteroids in acute myocardial infarction.

Forty-two patients admitted to the Coronary Care Unit with a diagnosis of acute myocardial infarction were studied within 24 hours of the onset of symptoms. In addition to therapy determined by the attending physician, there was a double-blinded administration of either a placebo or methylprednisolone, 30 mg/kg intravenously every 6 hours for four doses. This drug had no beneficial effect on infarct size, dysrhythmias, complications, or left ventricular function 2 weeks after infarction.

Creatine Kinase↗

Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep.

Symptoms suggesting autonomic instability and increased adrenergic effect were identified in 53 patients with primary disorders of impaired wakefulness. Urine and plasma catecholamine concentrations were significantly increased in patients with sleep apnea. Excessive increases in heart rate during isoproterenol infusions suggested adrenergic hyperresponsiveness as an alternative explanation for symptoms of catecholamine excess in some individuals. Twenty-two patients demonstrated mitral valve prolapse (MVP), implicating primary neurologic disturbances as potential factors in the fatigue and lassitude often associated with MVP. The catecholamine abnormalities may explain some of the difficulties frequently encountered in using stimulants to treat sleep disorders.

Adult↗

Beneficial effect of continuation of propranolol through coronary bypass surgery.

The safety and beneficial effect of continuation of propranolol (Pr) through coronary bypass surgery (CBS) was studied in two groups of patients. In the control group (50 patients) Pr was discontinued 24 h before CBS without reinstitution afterwards. In the propranolol group the drug was maintained up to 4 to 10 h before surgery and was restarted within 24 h afterwards. The incidence of subendocardial myocardial infarction was significantly lower in the Pr group (1 out of 30 vs 10 out of 50, p less than 0.05) while the incidence of transmural infarction was the same in both groups (3 out of 30, 10%, vs 5 out of 50, 10%). The incidence of supraventricular tachycardias during the first three postoperative days was significantly lower in the propranolol group compared to control (5% vs 30%, p less than 0.01). The 24 h urinary epinephrine and norepinephrine excretion was significantly greater than normal the day before surgery (136 +/- 12 vs 39 +/- 4 micrograms/24 h, p less than 0.01), and was still high two weeks after surgery (115.1 +/- 14 micrograms/24 h). There were no complications related to propranolol. The left ventricular function as measured from the systolic time intervals was the same pre- and postoperatively in both groups. The results of this study show that administration of propranolol up to 4 h before coronary bypass and reinstitution immediately afterwards is safe and beneficial.

Adult↗

Superiority of 24-hour outpatient monitoring over multi-stage exercise testing for the evaluation of syncope.

Twenty-four hour outpatient monitoring was compared with maximum multi-stage Treadmill exercise testing for the detection of dysrhythmias producing syncope or near syncope in 119 patients. All patients had cardiovascular disorders; only 21% had coronary artery disease. Patients with obvious cause of syncope and/or significant dysrhythmias by resting electrocardiograms (ECGs) were excluded. A significant dysrhythmia was found which was considered the probable cause of syncope or pre-syncope in 76 patients (64%). A non-cardiac cause was found in tachycardia, exercise testing identified only patients with complex ventricular dysrhythmias and missed 64% of these. Overall, dysrhythmias were found by ambulatory monitoring alone in 63 patients, by exercise testing alone in only three, and by both in 10. It is concluded that: 1) in the majority of patients with syncope or pre-syncope suspected to be of a cardiac origin, a dysrhythmia can be found; 2) ambulatory monitoring is far superior to exercise testing for detection of dysrhythmias; 3) exercise testing increases the yield for complex ventricular dysrhythmias.

Adolescent↗

Changes in diastolic time with various pharmacologic agents: implication for myocardial perfusion.

Diastolic time (DT) is calculated as the cycle length (RR) minus electromechanical systole (QS2). The ratio of DT (RR-QS2) to RR interval times 100, or the percent diastole (%D), varies nonlinearly with heart rate (HR), increasing rapidly with decreasing HR. The effect of commonly used cardioactive agents on %D was studied in five groups of normal subjects. In group 1 (n = 12), propranolol (160 mg daily) increased %D from 55.9 +/- 1.7 to 64.7 +/- 1.3 (p less than 0.001) by slowing HR. In group 2 (n = 12), dobutamine (2.5 micrograms/kg/min) increased %D from 56.4 +/- 1.4 to 61.8 +/- 1.3 (p less than 0.005) by shortening the QS2. In group 3 (n = 10), Cedilanid-D (1.6 mg i.v.) increased %D from 55.5 +/- 1 to 63.2 +/- 0.7 (p less than 0.001), both by slowing the HR and shortening the QS2. In group 4 (n = 12), isoproterenol (2 micrograms/min) increased HR and shortened the QS2 significantly. The net result was a significant reduction of %D from 56.1 +/- 1.4 to 53.5 +/- 1.1, (p less than 0.05). In group 5 (n = 15), a 100-mg bolus of i.v. lidocaine did not have a significant effect on %D. This study indicates that cardiovascular drugs may have significant effects on the relative duration of diastole either by affecting HR or the duration of systole. This may have clinical implications for patients with coronary artery disease and patients with left ventricular hypertrophy, since in both cases coronary flow in mostly diastolic.

Administration, Oral↗

Sleep apnea: treatment with protriptyline.

Fourteen patients with an average of more than 60 episodes of upper airway obstruction during night sleep were treated with a nonsedating tricyclic antidepressant, protriptyline. Frequency and duration of recorded apneas decreased in 11 cases, and satisfactory control of sleep apnea was maintained with medical therapy alone in 8 of these 11 patients for 7 to 15 months. Potential adverse effects of protriptyline, particularly on the cardiovascular system, limit its use in this illness. These results indicate the possibility of pharmacologic reversal of sleep-induced incoordination of the upper airway.

Adult↗