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Biomedical subjects

U Thadani

Publications and source records attributed to U Thadani.

At least 73 records · Page 4Linked to original sources
PubMed1987

Atenolol for ventricular ectopy: a dose-response study.

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.

Adult↗
PubMed1986

Rupture of abdominal aortic aneurysm during exercise. Gated blood pool studies.

There is a high prevalence of associated coronary artery disease in patients with abdominal aortic aneurysms. Exercise nuclear ventriculography is often used preoperatively to evaluate these patients. A patient who had a rupture of an abdominal aneurysm during exercise ventriculography is described. An instantaneous diagnosis of the acutely ruptured aneurysm was confirmed by blood pool scanning of the abdomen.

Aged↗
PubMed1986

Quantification of aortic regurgitation utilizing continuous wave Doppler ultrasound.

Aortic regurgitation and mitral stenosis are hemodynamically similar, insofar as both result in passive ventricular filling across a narrow orifice driven by a declining pressure gradient. Because mitral stenosis is successfully characterized by Doppler ultrasound determination of the velocity half-time, or time constant, aortic regurgitation might be quantified in an analogous fashion. Eighty-six patients with diverse causes of aortic regurgitation underwent continuous wave Doppler examination before cardiac catheterization or urgent aortic valve replacement. The Doppler velocity half-time was defined as the time required for the diastolic aortic regurgitation velocity profile to decay by 29%, whereas catheterization pressure half-time was calculated as the time required for transvalvular pressure to decay by 50%. Doppler velocity and catheterization pressure half-times were linearly related (r = 0.91). Doppler velocity half-times were inversely related to regurgitant fraction (r = -0.88). Angiographic severity (1+ = mild to 4+ = severe) was also inversely related to pressure and velocity half-time; a Doppler half-time threshold of 400 ms separated mild (1+, 2+) from significant (3+, 4+) aortic regurgitation with high specificity (0.92) and predictive value (0.90). The Doppler velocity half-time was independent of pulse pressure, mean arterial pressure, ejection fraction and left ventricular end-diastolic pressure. Estimation of transvalvular aortic pressure half-time utilizing continuous wave Doppler ultrasound is a reliable and accurate method for the noninvasive evaluation of the severity of aortic regurgitation.

Acute Disease↗
PubMed1986

Transdermal nitroglycerin patches in angina pectoris. Dose titration, duration of effect, and rapid tolerance.

The duration of effect of transdermal nitroglycerin patches was studied in 14 patients with angina pectoris. By titrating the dose to achieve specific circulatory effects, we chose a patch size that produced a consistent fall in systolic blood pressure of 10 mm Hg or greater for each patient (10 cm2 in 7 patients, 20 cm2 in 5, and 40 cm2 in 2; releasing 5, 10, and 20 mg of nitroglycerin per 24 hours, respectively). The effects of these individualized patches were compared with those of placebo patches. Compared with placebo, nitroglycerin patches increased exercise duration to the onset of angina (257 +/- 72 compared with 383 +/- 130 seconds, p less than 0.0001) and total exercise time (338 +/- 89 compared with 456 +/- 119 seconds, p less than 0.0001) and decreased ST segment depression (1.0 +/- 0.5 compared with 0.6 +/- 0.4 mm, p less than 0.05) at 4 hours but not at 24 and 48 hours. We conclude that nitroglycerin patches do not show objective evidence of antianginal or antiischemic effects for 24 hours. Tolerance to the circulatory and antianginal effects probably develops within 24 hours of patch application.

Administration, Topical↗
PubMed1986

Clinically silent atrial septal defects with evidence for cerebral embolization.

The cause of stroke in young patients frequently cannot be established. Eleven consecutive patients, age 50 and younger, had clinical evidence of cerebral embolization. Results of physical, radiographic, electrocardiographic, and two-dimensional echocardiographic examinations were normal in all patients. During normal respiration, eight of the patients had right-to-left shunts at the atrial level shown by microcavitation contrast two-dimensional echocardiography. Six of the eight patients with positive contrast studies had cardiac catheterization. Five of six patients had an atrial septal defect, normal right and left heart pressures, and small right-to-left shunts during a Valsalva strain. Four patients had surgical closure of the defect, which ranged in size from 5 to 10 mm. The remaining patients received anticoagulants. Interatrial communications appear to be common in young patients with stroke, suggesting paradoxical embolization as a possible mechanism. Contrast two-dimensional echocardiography should be done in such patients because it is the only noninvasive technique that reliably finds these defects.

Adolescent↗
PubMed1985

Comparative efficacy of 200, 300 and 400 mg of bepridil for chronic stable angina pectoris.

A total of 178 patients participated in a 14-week, multicenter, double-blind, parallel study to evaluate the comparative efficacy and safety of single daily doses of 200, 300 and 400 mg of bepridil hydrochloride and placebo in the treatment of patients with chronic stable angina pectoris. The results showed that weekly angina attacks and nitroglycerin consumption were significantly reduced from baseline levels with all doses of bepridil (p less than 0.01), and the reductions were consistently greater than those in the placebo group. For the 400-mg dose the reductions in angina attacks and nitroglycerin consumption were significantly greater (p less than or equal to 0.05) than those in the placebo group at all but 1 evaluation point. Exercise tolerance improved significantly during bepridil administration (p less than or equal to 0.05), and a significant linear dose response was noted for total exercise time, total work and time to onset of angina. In addition, bepridil was significantly superior to placebo for these parameters at doses of 300 (p less than or equal to 0.05) and 400 mg (p less than or equal to 0.01). There were small reductions in heart rate (mean 3.7 beats/min) and prolongation of QT and QTc intervals (approximately 30 to 40 milliseconds) associated with bepridil treatment. Bepridil was well tolerated by patients in this study. When adverse effects occurred, they most frequently involved the gastrointestinal and central nervous systems. Of the patients receiving bepridil, 6% discontinued therapy because of adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Assessment of "optimal" beta blockade in treating patients with angina pectoris.

Assessment of optimal beta blockade in treating patients with angina pectoris remains a challenge. Reduction in resting heart rate is a poor guide to therapy; the dose response curves are flat and drugs with intrinsic sympathomimetic activity may not lower resting heart rates despite their efficacy. Log plasma concentrations of beta blockers correlate with reduction in exercise tachycardia but not with improvement in exercise tolerance of reduction in myocardial ischaemia. Although useful, reduction in frequency of anginal attacks and nitroglycerin consumption during therapy is a poor guide in assessing optimal beta blockade. The best way to assess optimal therapy is to demonstrate maximum increase in exercise performance in association with reduction in myocardial ischaemia and adequate suppression of exercise-induced increase in heart rate and blood pressure. This requires repeated exercise testing at multiple work loads after various doses of the drug until there is no further increase in exercise duration or reduction in heart rate. When given in optimal and equipotent doses all beta blockers are equally effective antianginal agents and can be prescribed twice daily.

Adrenergic beta-Antagonists↗
PubMed1985

Anti-anginal and anti-ischemic efficacy of conventional and slow release formulations of isosorbide-5-mononitrate in angina pectoris.

Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioavailable after oral administration. Following administration of single oral doses of 10 to 50 mg, isosorbide-5-mononitrate exerts beneficial hemodynamic, anti-ischemic and anti-anginal effects within 30 to 45 minutes and the effects persist for several hours. During sustained therapy with conventional formulation, persistent anti-ischemic and anti-anginal effects have been reported when the drug is given in a dose of 20 mg two or three times a day. However, tolerance to anti-anginal and anti-ischemic effects develops rapidly if used in higher doses of 50 mg three times a day. Tolerance to anti-anginal effects within 20 hours of administration of a single oral dose of 100 mg, slow release isosorbide-5-mononitrate has been reported. Further, no improvement in exercise tolerance or ST segment depression could be documented at 4, 20 or 24 hours after therapy for one week with either 50 or 100 mg slow release isosorbide-5-mononitrate once a day. From the available reports, the most effective way to prescribe isosorbide-5-mononitrate for angina pectoris appears to be the conventional formulation in a dose of 20 mg two or three times a day.

Angina Pectoris↗
PubMed1984

Nitrates for angina pectoris. A critical review of therapeutic efficacy and tolerance.

Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.

Angina Pectoris↗
PubMed1983

Beta blockers in hypertension.

Beta-adrenoceptor antagonists are effective in the management of patients with mild-to-moderate hypertension. Noncardioselective agents, cardioselective agents and beta blockers with intrinsic sympathomimetic activity (ISA) are equally effective, provided they are used in equipotent doses. Beta blockers can be used as first-line therapy in the management of hypertension and can be safely combined with diuretics, vasodilators, or both, for a better control of blood pressure. The exact mechanism by which beta blockers decrease blood pressure remains speculative, but they all reduce cardiac output during long-term therapy; drugs with ISA lower cardiac output and heart rate less than do drugs without ISA. Pharmacokinetic properties of beta blockers differ widely; drugs metabolized by the liver have shorter plasma half-lives than drugs primarily excreted by the kidneys. Although many of the side effects of various beta blockers are similar, differences in water and lipid solubility account for a higher incidence of central nervous system side effects with lipid-soluble drugs (such as propranolol and metoprolol) than with hydrophilic drugs (such as atenolol and timolol). The incidence of cold extremities has been reported to be less with drugs with ISA, and the incidence of bronchospasm less with cardioselective drugs. In the management of uncomplicated mild-to-moderate hypertension, all beta blockers are equally effective and produce less troublesome side effects than alternative antihypertensive agents. For effective therapy beta blockers can be used in 2 divided daily doses or even once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1983

Interaction of indomethacin and nitroglycerin on hemodynamics and exercise tolerance in patients with angina pectoris.

The influence of indomethacin therapy on the circulatory and antianginal effects of nitroglycerin were studied in six patients with stable angina pectoris. Indomethacin 50 mg or identical placebo capsules were administered three times a day for 1 week each in a double-blind, random manner. Heart rate, blood pressure, and ST-segment depression were measured at rest and during exercise before and after the administration of 0.6 mg sublingual nitroglycerin during indomethacin and placebo therapy. Nitroglycerin lowered standing systolic blood pressure by 38 mm Hg during placebo therapy (p less than 0.001) and by 36 mm Hg during indomethacin therapy (p less than 0.001). This was accompanied by a reflex increase in heart rate (p less than 0.001) which was of similar magnitude during placebo and indomethacin therapy. The increase in exercise duration to the onset of angina post nitroglycerin was similar during placebo and indomethacin therapy (128 vs 84 s; NS). Similarly, the increase in the total duration of exercise post nitroglycerin was similar during placebo and indomethacin therapy. Reduction in ST-segment depression post nitroglycerin was more pronounced during placebo than indomethacin therapy, but did not achieve statistical significance. The results show that indomethacin did not modify the circulatory effects of nitroglycerin at rest or during exercise and did not attenuate the increase in exercise tolerance produced by sublingual nitroglycerin. Since indomethacin is a potent prostaglandin inhibitor, the findings indirectly suggest that the vasodepressor and antianginal effects of nitroglycerin are in all probability not mediated by prostaglandins.

Aged↗
PubMed1982

Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy.

The effects of different oral doses of isosorbide dinitrate administered acutely and four times daily during sustained therapy were studied in 12 patients with angina pectoris. After administration of 30, 60 and 120 mg of isosorbide dinitrate, the average plasma concentrations were higher and the area under the plasma concentration time curve was greater during sustained than during acute therapy (p less than 0.01). Reduction in standing systolic blood pressure was greater during acute than during sustained therapy (p less than 0.001). This reduction in systolic blood pressure was dose-related and persisted for 8 hours during acute therapy, but was not dose-related and was demonstrable for only 4 hours during sustained therapy. Compared with placebo therapy, exercise duration to the onset of angina and to the development of moderate angina increased significantly after each dose of isosorbide dinitrate for 8 hours during acute therapy but for only 2 hours during sustained therapy. During acute therapy, administration of a single dose of 15 or 30 mg of isosorbide dinitrate produced similar improvement in exercise tolerance as did a dose of 60 or 120 mg. During sustained therapy (15 mg four times daily), exercise tolerance increased to the same magnitude as with doses of 30, 60 or 120 mg four times daily. In most patients, near maximal improvement in exercise tolerance occurred after a dose of 15 or 30 mg four times daily. It is concluded that during sustained therapy with isosorbide dinitrate, partial tolerance to the antianginal and circulatory effects develops rapidly.

Administration, Oral↗
PubMed1982

Beta adrenergic blocking agents for exertional angina pectoris.

Beta adrenergic blocking agents are effective antianginal agents and reduce the frequency of anginal attacks, nitroglycerin consumption, and improve exercise tolerance in patients with stable exertional angina pectoris. These drugs are effective in the management of exertional angina pectoris primarily due to their ability to block beta 1 receptors and thereby competitively blocking the effects of sympathetic stimulation (i.e. increase in myocardial oxygen demand) during exercise. In this report other pharmacological properties of these agents i.e. membrane stabilizing activity, intrinsic sympathomimetic activity and cardioselectivity are of little importance. Comparative studies with beta adrenergic blocking agents with different ancillary properties, utilizing intravenous preparations, acute single and multiple oral dosing and sustained oral therapy prescribed for several weeks or months, show that if used in equipotent doses all beta adrenergic blocking agents are equally effective antianginal agents. It should be recognized that therapy with these agents may precipitate heart failure or aggravate bronchospasm in susceptible patients. This can occur with cardioselective agents and with beta blockers which also have intrinsic sympathomimetic activity.

Administration, Oral↗
PubMed1982

Influence of attenuation on radionuclide stroke volume determinations.

Using a method for determination of absolute volumes, including correcting for attenuation, we have explored the ability of the method to determine stroke volume in humans by radionuclide techniques. Thermodilution cardiac output determinations and multigated equilibrium blood-pool scintigraphy in the LAO view were performed simultaneously in twenty patients in which no evidence of intracardiac shunts or valvular disease was present. The correlation was good between the attenuated radionuclide and thermodilution stroke volume (r = 0.80, s.e.e. of estimate = 12 ml; SVtd = 2.31 x SVr + 18 ml). When correction for attenuation was made, the correlation improved (r = 0.96, s.e.e. = 6 ml) and approached the line of identity (SVtd = 0.99 x SVr + 1.2 ml). The correlation was also good between radionuclide cardiac output, corrected for attenuation, and the thermodilution cardiac output (r = 0.89, s.e.e. = 0.36 l/min; COtd = 0.86 x COr + 0.67 l/min). Thus our method of correction for attenuation in the determination of absolute left-ventricular volumes has been shown to provide a reliable, noninvasive means of calculating stroke volume and cardiac output in humans, without the use of geometric assumptions or regression equations.

Cardiac Output↗
PubMed1981

Hemodynamic effects of disopyramide at rest and during exercise in normal subjects.

The hemodynamic effects of disopyramide phosphate, 2.0 mg/kg body weight, given intravenously over a period of five minutes were studied at rest and during exercise in ten patients without clinical or angiographic evidence of heart disease. Following disopyramide, the resting cardiac index was lower (4.0 +/- 0.6 vs 4.3 +/- 0.6 liters/min/m2, mean +/- 1 SD,P less than 0.05), while left ventricular end-diastolic pressure (16 +/- 4 vs 11 +/- 4 mm Hg, P less than 0.001), pulmonary arterial (PA) mean pressure (20 +/- 5 vs 17 +/- 5 mm Hg, P less than 0.05), and brachial arterial (BA) mean pressure (105 +/- 8 vs 96 +/- 7 mm Hg, P less than 0.05), were higher than the pre-infusion resting values. During exercise, there was no change in left ventricular end-diastolic pressure while cardiac index rose from 4.0 +/- 0.6 to 6.5 +/- 0.6 liters/min/m2 (P less than 0.001) and left ventricular stroke work index increased from 62 +/- 19 to 84 +/- 22 gm/beat/m2 (P less than 0.001). The normal hemodynamic response during exercise after disopyramide despite the apparent depression of left ventricular function at rest probably reflects the positive inotropic effect of enhanced sympathoadrenergic activity.

Adult↗
PubMed1981

Slow release oxprenolol in angina pectoris: study comparing oxprenolol, once daily, with propranolol, four times daily.

Oxprenolol and propranolol are noncardioselective beta adrenoreceptor blocking agents known to be equally effective in the management of patients with angina pectoris. Both are usually prescribed four times daily. Slow release formulation of oxprenolol administered once daily has been shown to maintain therapeutic effects for 24 hours. In a double-blind crossover study in 23 patients with stable angina pectoris, the effects of 160 mg slow release oxprenolol, administered once daily for 1 month, were compared with those of 40 mg of propranolol given four times daily for a similar period. No adverse effects occurred when patients were switched between treatment schedules. The average number of anginal attacks experienced were 11/month during oxprenolol therapy and 8/month during propranolol therapy (difference not significant). The resting values for heart rate were higher 7 1/2 nd 24 hours after oxprenolol than they were 4 and 12 hours after propranolol (p less than 0.01). The treadmill walking time to the onset of angina and to the development of moderate angina 24 hours after oxprenolol was less than that observed 7 1/2 hours after the drug or 4 and 12 hours after propranolol (p less than 0.01). In contrast, the values for walking time to the onset of angina and to the development of moderate angina at 4 and 12 hours after propranolol were similar. This decreased exercise tolerance 24 hours after oxprenolol was associated with a lesser degree of beta adrenoreceptor blockade than that present after propranolol as documented by higher levels of heart rate (p less than 0.05), systolic blood pressure (p less than 0.05) and rate-pressure product (p less than 0.05) during exercise after oxprenolol therapy. It is concluded that in the doses used, slow release oxprenolol administered once daily does not exert as consistent a beneficial effect on exercise tolerance throughout the dosing schedule as does propranolol given four times daily.

Adult↗