Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Noninvasive assessment by radionuclide angiocardiography

doi:10.1016/0002-9343(78)90741-6

The American Journal of Medicine

Volume 65, Issue 6, December 1978, Pages 903-910

https://doi.org/10.1016/0002-9343(78)90741-6 Get rights and content

Abstract

Although aminophylline is a widely used bronchodilator in chronic obstructive pulmonary disease (COPD), its effects upon cardiac performance have not been fully established. The effect of aminophylline upon right ventricular and left ventricular ejection fraction and the left ventricular ejection rate was evaluated by first-pass quantitative radionuclide angiocardiography in 15 patients with COPD, including four with cor pulmonale, and in five control subjects without cardiopulmonary disease. Aminophylline infusion (9 mg/kg) significantly increased the right ventricular ejection fraction (45 to 52 per cent), left ventricular ejection fraction (60 to 67 per cent) and left ventricular ejection rate (3.4 to 4.1 sec⁻¹) in patients with COPD (all parameters, p < 0.001). In six of eight patients with depressed control right ventricular performance, right ventricular ejection fraction normalized and in two of five patients with depressed control left ventricular performance, the left ventricular ejection fraction and left ventricular ejection rate normalized. In control subjects, comparable increases were noted in the right ventricular ejection fraction (50 to 56 per cent), left ventricular ejection fraction (62 to 71 per cent) and left ventricular ejection rate (3.2 to 4.6 sec⁻¹) (p < 0.001). One-second forced expiratory volume (FEV₁) and forced vital capacity (FVC) increased significantly in patients with COPD but not in control subjects. Arterial carbon dioxide tension decreased significantly in both groups (p < 0.05), whereas arterial oxygen tension did not change. Theophylline blood levels did not correlate with absolute increases in right ventricular or left ventricular ejection fraction.

These data indicate that aminophylline acutely enhances biventricular performance in COPD. Since comparable cardiovascular changes are induced in normal subjects in whom ventilatory function was not altered, the beneficial effects of aminophylline upon global ventricular performance appear to be independent of the degree of pulmonary compromise.

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Cited by (88)

Barry Lewis Zaret, MD: A conversation with the editor
2005, American Journal of Cardiology
Theophylline: Recent advances in the understanding of its mode of action and uses in clinical practice
1998, Mayo Clinic Proceedings
Theophylline, a drug that has been used for several decades, has several different actions at a cellular level, including inhibition of phosphodiesterase isoenzymes, antagonism of adenosine, enhancement of catecholamine secretion, and modulation of calcium fluxes. Recently, theophylline was found to have several immunomodulatory and anti-inflammatory properties, and thus interest in its use in patients with asthma has been renewed. The use of theophylline in the treatment of asthma and chronic obstructive pulmonary disease has diminished with the advent of new medications, but theophylline remains beneficial, especially in the patient with difficult refractory symptoms. In the future, theophylline may be used as treatment for bradyarrhythmias after cardiac transplantation, prophylactic medication to reduce the severity of nephropathy associated with intravenous administration of contrast material, therapy for breathing problems during sleep, and treatment for leukemias.
The use of bronchodilators in stable chronic obstructive pulmonary disease
1997, Pulmonary Pharmacology and Therapeutics
Optimizing the method to calculate right ventricular ejection fraction from first-pass data acquired with a multicrystal camera
1995, Journal of Nuclear Cardiology
Background. The advantage of radionuclide angiographic techniques used to measure rightventricular ejection fraction (RVEF) is geometry independence, but the weakness is right atrial (RA) overlap. To minimize the effect of RA counts on right ventricular time activity curve (TAC), two regions of interest (ROI), one drawn for the end-diastolic image and one for the end-systolic image, are used for the calculation of RVEF from equilibrium gated blood pool scans (GBPS) and from gated first-pass studies with an Anger camera. A multicrystal camera offers both temporal separation of the bolus to the right side of the heart and good count statistics; therefore first-pass studies performed on a multicrystal camera theoretically should yield the most accurate measurements of RVEF, but few studies have been performed to validate RVEF against a reliable gold standard.
Methods and Results. To develop and validate an accurate method to measure RVEF from multicrystal first-pass data, 25 patients underwent sequential cine-MRI, first-pass radionuclide angiography, and gated equilibrium imaging. Five additional healthy volunteers underwent cine-MRI alone. Right and left ventricular volumes were measured from serial short axis cine-MRI views according to Simpson's rule. Three methods were used to calculate RVEF from first-pass data: a single ROI method, a dual ROI method, and a method in which a single ROI is applied to RA subtracted first-pass dynamic data. Five additional healthy volunteers underwent cine-MRI alone. When right ventricular stroke volume was plotted versus left ventricular stroke volume for the 5 volunteers and the 15 patients without valvular regurgitation, the regression line was not significantly different from the line of identity, supporting the accuracy of cine-MRI to measure RVEF. The RVEF by cine-MRI ranged from 34% to 59%; first-pass RVEF with a single ROI from 26% to 48%; first-pass RVEF with two ROIs from 31% to 59%; first-pass RVEF with RA subtracted single ROI from 29% to 60%; and RVEF from GBPS with multiple ROIs from 28% to 55%. The regressions for all three of the first-pass methods versus cine-MRI were significant (p<0.01) as was the regression for the equilibrium GBPS versus cine-MRI but the correlation was weaker. The regressions for the 2-ROI method and for the RA subtracted single ROI method were not significantly different from the line of identity, whereas the regressions for both the single ROI method and for equilibrium GBPS were significantly different from the line of identity (p<0.01).
Conclusions. Cine-MRI can be used to validate radionuclide algorithms. Of the four radionuclide methods for measuring RVEF that were assessed, the first-pass 2-ROI method and the first-pass RA subtracted single ROI are the most accurate, the first-pass single ROI method underestimates RVEF, and the RVEF values measured from GBPS are less accurate.
Dose dependency of aminophylline effects on hemodynamic and ventricular function in patients with chronic obstructive pulmonary disease
1993, Chest
The effects of aminophylline on pulmonary vascular tone, systemic hemodynamics, and ventricular ejection fractions reported in the literature show some discrepancies. We therefore studied in COPD patients the effects of aminophylline on hemodynamics, on ventricular ejection fractions, and on systolic and diastolic functions of each ventricle, and we measured simultaneously the blood level of the drug. The analysis of the data revealed a relationship between the blood level of aminophylline and the variations of right ventricular ejection fraction (RVEF) (r = 0.83, p = 0.005), left ventricular ejection fraction (LVEF) (r = 0.76, p = 0.017), pulmonary vascular resistance index (PVRI) (r = –0.58, p = 0.096), systemic vascular resistance index (SVRI) (r= –0.60, p = 0.08), and right ventricular peak systolic pressure/end-systolic volume index (RVPSP/ESVI) (r=0.75, p=0.02). Modifications of ejection fractions and vascular resistance indices were correlated for both ventricles (RVEF vs PVRI, r= –0.77, p=0.01; LVEF vs SVRI, r= –0.76, p=0.02). Finally, RVEF modification was also correlated to RVPSP/ESVI variation (r=0.78, p=0.01). These results suggest that even within the therapeutic range (10 to 20 mg/L), the effects of aminophylline seemed to depend on its blood level. This dose dependency could explain the contradictory data reported in the literature concerning the effects of aminophylline on pulmonary and systemic hemodynamics and on ventricular function.
(Chest 1993; 103:1725-31)
Right ventricular function at rest and during exercise in chronic obstructive pulmonary disease
1992, Chest
Right ventricular ejection fraction (RVEF), a measure of systolic pump performance of the right ventricle, is frequently depressed at rest or during exercise in patients with chronic obstructive pulmonary disease (COPD). The most common cause of reduced RVEF in COPD is augmentation of right ventricular afterload, namely an increase in pulmonary artery pressure and pulmonary vascular resistance. Therapy with agents that decrease the afterload on the right ventricle have the potential to improve the systolic performance of this chamber. Oxygen, vasodilators such as hydralazine and nifedipine, theophylline, and sympathomimetics all may augment RVEF in part by reducing pulmonary vascular resistance and, in some cases, pulmonary artery pressures in patients with COPD and cor pulmonale. However, only oxygen therapy has been shown to improve survival.

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^☆: This study was supported in part by NHLBI Contract No. 1HV52977 and NHLBI Grant R01HL21690-01. This work was presented in part at the Annual Meetings of the American Federation for Clinical Research, May 1977, and the American Thoracic Society, May 1977.

^∗: Young Investigator, National Heart, Lung, and Blood Institute.

¹: From the Cardiology and Pulmonary Sections, Department of Internal Medicine, and the Nuclear Medicine Section, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.

^†: Established Investigator, American Heart Association.

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Clinical studyEffects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Noninvasive assessment by radionuclide angiocardiography☆

Abstract

Am J Cardiol

Med Clin North Am

Chest

Am J Med

N Engl J Med

Br Heart J

Am Heart J

Am Rev Respir Dis

The pharmacokinetics of theophylline: application to adjustment of the clinical dose of aminophylline

Clin Pharmacol Ther

Rational intravenous dose of theophylline

N Engl J Med

Intravenous aminophylline dosage

JAMA

Effect of aminophylline on ventilatory response in normal man

Am Rev Respir Dis

Central nervous system stimulants: The xanthines

Hemodynamic effects of aminophylline in chronic obstructive pulmonary disease

Circulation

Hemodynamic effects of aminophylline in cor pulmonale

Circulation

Effects of aminophylline on the pulmonary circulation and left ventricular performance in patients with valvular heart disease

Circulation

Effect of aminophylline on the respiration and pulmonary circulation

Clin Sci

Clinical study
Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Noninvasive assessment by radionuclide angiocardiography☆