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Biomedical subjects

H Boudoulas

Publications and source records attributed to H Boudoulas.

At least 73 records · Page 4Linked to original sources
PubMed1990

Rest and exercise cardiovascular effects of terazosin in congestive heart failure.

This study investigated the acute effects of the alpha 1 antagonist terazosin on myocardial circulatory responses at rest and during exercise. Ten patients with congestive heart failure (class III and IV) underwent hemodynamic evaluation before and after a 5-mg oral dose of terazosin. At rest and during exercise, terazosin significantly decreased pulmonary capillary wedge pressure, systemic vascular resistance and mean arterial pressure while cardiac index increased. Stroke volume index increased (p less than 0.01) during exercise while left ventricular stroke work index remained unchanged in both experimental conditions. Terazosin administration significantly decreased both rest and exercise myocardial oxygen consumption while exercise coronary sinus oxygen content increased and arterial-coronary sinus oxygen difference diminished (p less than 0.05). Parallel with these changes, alpha blockade decreased the ratio of coronary blood flow to total cardiac output. Coronary vascular resistance remained unaltered with alpha blockade both at rest and during exercise. Coronary blood flow tended to diminish with decreased myocardial oxygen demand. Alpha 1 blockade induces systemic vasodilation and improves myocardial circulatory parameters without inducing coronary dilation or altering metabolic autoregulation.

Adrenergic alpha-Antagonists↗
PubMed1990

Comparison of hypersensitivity to adrenergic stimulation after abrupt withdrawal of propranolol and nadolol: influence of half-life differences.

To test whether a beta-blocker's pharmacokinetics has an effect on the development of the beta-blocker withdrawal syndrome, we compared response to exercise and isoproterenol after abrupt withdrawal of two beta-blockers, one with a short half-life (propranolol) and one with a long half-life (nadolol). Eight normal males participated in the randomized cross-over trial. They took propranolol, 40 mg every 6 hours for 6 days, and nadolol, 80 mg daily for 7 days. Exercise- and isoproterenol-induced changes in heart rate and pulse pressure were significantly less than control values during treatment with both drugs (p less than 0.05). Significant hypersensitivity of heart rate response was seen on days 2, 3, and 7 after propranolol withdrawal (p less than 0.05) and on day 6 after nadolol withdrawal (p less than 0.005). Hypersensitive responses to isoproterenol were seen after propranolol withdrawal; no evidence of hypersensitivity to isoproterenol was seen after nadolol withdrawal. The area under the heart rate response, time curve after nadolol withdrawal was significantly less than that after propranolol withdrawal (20.3 beats/min.day vs 44.9 beats/min.day, respectively, (p less than 0.05). There was a significant inverse correlation between the degree of hypersensitivity and nadolol pharmacokinetic half-life (r = -0.80, p less than 0.02). We conclude that abrupt withdrawal of a beta-blocker with a long half-life may protect against the development of the beta-blocker withdrawal syndrome.

Adult↗
PubMed1990

New coronary artery disease index based on exercise-induced QRS changes.

Exercise-induced changes in Q, R, and S wave amplitudes have been reported to detect coronary artery disease but with low specificity, low sensitivity, or both; it was hypothesized that their incorporation into a composite index (Athens QRS score) might improve specificity and sensitivity. For this purpose 246 patients were analyzed retrospectively and 160 prospectively. All patients underwent maximal exercise testing with a standard Bruce protocol and coronary arteriography as part of the diagnostic evaluation for possible or definite coronary artery disease. The Athens QRS score was decreased as the number of obstructed coronary arteries increased (normal coronary arteries = 7.85 +/- 5.23 mm, one-vessel disease = 5.2 +/- 5.3 mm, two-vessel disease = -0.85 +/- 5.4 mm, three-vessel disease = -3.5 +/- 5.8 mm; p less than 0.0001); the score was unrelated to exercise-induced ST segment depression, and negative (less than 0) scores were always associated with coronary artery disease. An Athens QRS score of 5 mm predicted coronary artery disease with sensitivity ranging from 75% to 86% and a specificity ranging from 73% to 79%, values higher than those of the Q wave (75% and 50%, respectively), R wave (65% and 55%), and S wave (70% and 10%) and of the ST segment depression (62% and 70%). It is concluded that exercise-induced changes in the QRS complex provide a useful index not only for the diagnosis but also for the assessment of severity of coronary artery disease.

Angiography↗
PubMed1990

Mitral stenosis: left atrial dynamics reflect altered passive and active emptying.

To assess the passive and the active phases of left atrial (LA) emptying, LA volumes and function were studied in 15 patients with mitral stenosis (MS) in sinus rhythm and in 11 normal subjects (NL) with two-dimensional echocardiography with simultaneous electrocardiograms. LA and left ventricular (LV) volumes were measured with the biplane area-length method. LA maximal and minimal volumes were measured at mitral valve opening and closure, respectively. In addition, LA volume was measured at onset of atrial systole (beginning of the P wave on the electrocardiogram). LA volumes were larger in MS compared with NL; Maximal 122 +/- 65 cm3 versus 46 +/- 12 cm3, p less than 0.001; onset of atrial systole 108 +/- 63 cm3 versus 29 +/- 12 cm3, p less than 0.001; minimal 90 +/- 60 cm3 versus 18 +/- 7 cm3, p less than 0.001. LA passive emptying volume (maximal minus volume at onset of atrial systole) was not statistically different in MS compared with NL, while LA active emptying volume (volume at onset of atrial systole minus minimal) was larger in MS compared with NL (17 +/- 5 cm3 versus 11 +/- 5 cm3, p less than 0.05). The net result was normal LA total emptying volume (maximal minus minimal) MS 32 +/- 11 cm3, NL 28 +/- 5 cm3. In contrast, the LA emptying fractions were significantly decreased in MS compared with NL (passive 0.13 +/- 0.08 versus 0.39 +/- 0.1, p less than 0.0001, active 0.19 +/- 0.08 versus 0.38 +/- 0.07, p less than 0.0001, total 0.30 +/- 0.1 versus 0.62 +/- 0.07, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Mitral valve prolapse: cardiac arrest with long-term survival.

Cardiac arrest has been reported in patients with mitral valve prolapse; however, clinical characteristics and survival information are limited since most of the cases reported include autopsy data. Nine patients (2 male, 7 female) with mitral valve prolapse were identified who had cardiac arrest; ventricular fibrillation was documented in 8 patients; resuscitation was unsuccessful in 2. Eight had a history of palpitations (months to 15 years duration) and ventricular arrhythmias, 3 had a history (5-15 years) of recurrent syncope, and 1 was totally asymptomatic. Cardiac catheterization-angiographic studies in 8 patients demonstrated normal coronary artery anatomy and mitral valve prolapse. All 9 patients had auscultatory and echocardiographic evidence of mitral valve prolapse. Seven survivors (6 still alive) were followed from 3 to 14 years after cardiac arrest. A subset of patients with mitral valve prolapse and cardiac arrest is described in whom past medical history is compatible with cardiac arrhythmias or syncope, and whose long-term prognosis appears better than patients with other causes of cardiac arrest.

Adult↗
PubMed1990

Comparison of single-dose and steady-state nadolol plasma concentrations.

The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected beta-blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUC0-tau at steady state was greater than the AUC0-infinity following a single dose in five of the six subjects. The mean ratio of AUCss/AUCsd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol.

Adult↗
PubMed1990

Systolic time intervals.

The systolic time intervals (STI) offer temporal description of the sequential phases of cardiac cycle which are influenced physiologically by the same variables as affect other measures of left ventricular (LV) performance. The STI hence offer a measure of ventricular function which augments other measures of ventricular performance. Because of the extreme sensitivity of this variable and the ease of its measurement the STI are well suited for studying the effect of pharmacologic agents upon the heart.

Cardiac Output↗
PubMed1990

Distensibility of the ascending aorta: comparison of invasive and non-invasive techniques in healthy men and in men with coronary artery disease.

Distensibility of the ascending aorta, measured non-invasively, was compared with values obtained by invasive techniques in 46 males (30 patients with coronary artery disease and 16 age-matched normal subjects). Aortic diameters were measured at a level 3 cm above the aortic valve using both echocardiographic and angiographic techniques. Aortic distensibility was calculated from the aortic diameters and aortic pressure or brachial artery pressure using the formula: 2 x (change in aortic diameter)/(diastolic aortic diameter) x (change in aortic pressure). Distensibility of the ascending aorta determined non-invasively was closely related to that obtained by direct measurements (r = 0.949, P less than 0.001). Patients with coronary artery disease had similar pressures, but markedly lower distensibility than normal subjects, as shown by both invasive and non-invasive techniques. The results indicate that aortic distensibility in patients with coronary artery disease can be obtained non-invasively with a high degree of accuracy.

Adult↗
PubMed1990

Antiarrhythmic activity and unbound concentrations of disopyramide enantiomers in patients.

Six patients with reproducible inducible atrial flutter randomly received, in double-blinded fashion, 77 mg of S(+)-disopyramide and R(-)-disopyramide over 20 min by intravenous infusion on two occasions separated by at least 24 h. The S(+) enantiomer prevented the inducibility of atrial flutter in five of the six patients; atrial flutter was inducible following R(-) enantiomer administration in all six patients (p less than 0.05). The mean (+/- SD) antiarrhythmic unbound serum concentration range of S(+)-disopyramide was 0.55 +/- 0.31-0.90 +/- 0.81 mg/L. The binding of disopyramide was stereoselective: the mean unbound fractions of S(+)- and R(-)-disopyramide were 0.207 +/- 0.119 and 0.338 +/- 0.214 (p less than 0.05). Binding of the individual enantiomers in some patients was markedly concentration dependent. The data suggest that the antiarrhythmic activity associated with racemic disopyramide resides in the S(+) enantiomer.

Anti-Arrhythmia Agents↗
PubMed1990

The pharmacokinetics of midazolam in patients with congestive heart failure.

The disposition of midazolam was investigated in six patients with congestive heart failure (CHF) and six age- and weight-matched healthy subjects by administering two single doses of the drug (3.75 mg i.v. and 7.5 mg p.o.) separated by 1 week. Serial blood samples were collected for 24 h after each dose and plasma was assayed for midazolam by GC-MS. In the CHF patients, the elimination half-life was prolonged (4 to 4.5 vs less than 3 h), the systemic clearance was lowered (376 vs 551 ml min-1) and the peak plasma drug concentration after the p.o. dose was higher (76 vs 42 ng ml-1). The systemic availability (45 vs 41%), the steady state volume of distribution (111 vs 108 l) and the time of peak plasma drug concentration after the p.o. dose (0.9 vs 0.9 h) were unchanged. The predominant effect of CHF was on the clearance of midazolam which was decreased by 30%. The drug was well tolerated and did not cause any adverse effects.

Adult↗
PubMed1989

Drug- or hormone-induced adaptation: model of adrenergic hypersensitivity.

A pharmacokinetic/pharmacodynamic model of hypersensitivity to adrenergic stimulation following abrupt withdrawal of chronic beta blockade was developed. The model employs the Hill equation, a term which describes the competition between isoproterenol and l-propranolol for beta receptors, and a kinetic term which characterizes the appearance and disappearance rates of up-regulated beta receptors. The model predicted peak chronotropic hyperresponsiveness to isoproterenol 48 hr following abrupt withdrawal of chronic treatment with daily propranolol doses of 160 mg, and a drug half-life of 3.5 hr. The model also predicted that increasing the dose rate and prolonging the half-life of propranolol delayed and decreased the extent of adrenergic hypersensitivity. The time-course of adrenergic hypersensitivity simulated by our model was in excellent agreement with that observed in studies which were published earlier by our laboratory. The model underestimated the extent of adrenergic hypersensitivity. The results of our simulation are consistent with a beta agonist-receptor-effector system, which involves spare receptors, amplification of response by second and third messengers, and beta agonist- antagonist-induced receptor regulation.

Adaptation, Physiological↗