Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon.

OBJECTIVES: The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease. BACKGROUND: Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent. METHODS: In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 +/- 1.0 mg/liter (low), 8.2 +/- 1.8 mg/liter (medium) and 13.2 +/- 2.3 mg/liter (high). RESULTS: Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations. CONCLUSIONS: It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease.

Comparison of dobutamine and exercise using technetium-99m sestamibi imaging for the evaluation of coronary artery disease.

Studies using dobutamine thallium-201 myocardial perfusion imaging have suggested a high sensitivity and specificity for the detection of coronary artery disease. However, few data are available comparing dobutamine with exercise stress for the detection and localization of perfusion defects. This study compared the effects of dobutamine and exercise stress using technetium-99m sestamibi single-photon emission computed tomographic imaging in the same patients in a prospective crossover trial. Twenty-four patients with a high likelihood of coronary artery disease underwent tomographic myocardial imaging at rest, after symptom-limited treadmill exercise, and after intravenous dobutamine (maximum 30 micrograms/kg/min). Tomograms of the left ventricle were divided into 20 segments and were interpreted without knowledge of patient identity or stress protocol. Dobutamine was well tolerated by all patients. Segment-by-segment concordance between exercise and dobutamine images was highly significant (kappa = 0.56, p < 0.0001). Global first-order agreement (normal vs abnormal) between exercise and dobutamine studies was 96% (kappa = 0.65, p = 0.02); global second-order agreement (normal vs fixed vs ischemic defect) was 88% (kappa = 0.45, p = 0.02). Regional first- and second-order agreement were 96 and 93%, respectively (p < 0.001 for both). Twenty patients underwent coronary angiography. Comparisons between exercise and angiography and between dobutamine and angiography were similar for both global agreement (95 vs 100%, p = NS) and regional agreement (77 vs 72%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of right ventricular perfusion defects after inferior myocardial infarction assessed by low-level exercise with technetium 99m sestamibi tomographic myocardial imaging.

To assess the prevalence of right ventricular perfusion defects after a recent inferior wall myocardial infarction, 33 patients were studied 6 to 14 days after infarction with low-level exercise testing and technetium 99m (99mTc) sestamibi (SPECT) imaging. Twenty-two control subjects with a < 5% likelihood of coronary artery disease undergoing exercise 99mTc sestamibi imaging were also studied. For each image the right ventricle was computer isolated from reconstructed transverse cardiac slices, followed by reorientation into oblique slices. Both right and left ventricular images were visually assessed for defects. A quantitative method of defect detection was also applied to the right ventricle. For the right ventricle, 100% of the stress images and 96% of the rest images were adequate for interpretation. Right ventricular stress perfusion defects were identified in 10 (30%) of 33 patients with recent inferior infarction, with 50% completely or partially normalizing on rest images, consistent with ischemia. Of 14 patients with left ventricular inferoseptal defects, eight (57%) had right ventricular defects compared with 2 (11%) of 19 without inferoseptal defects (p < 0.005). We concluded that the right ventricle can be adequately assessed for perfusion defects by means of exercise with 99mTc sestamibi SPECT imaging. Defects of the right ventricle after inferior myocardial infarction occur frequently, and many have evidence of ischemia. Right ventricular perfusion defects are closely associated with left ventricular inferoseptal defects.

Pretreatment with theophylline does not affect adenosine-induced thallium-201 myocardial imaging.

This study was designed to evaluate the effects of intravenous theophylline given before intravenous adenosine for thallium-201 imaging. Sixteen patients with known reversible thallium-201 defects were randomized to a double-blind crossover study of a 45-minute infusion of placebo or theophylline (given as the ethylenediamine salt, aminophylline, mean concentration 16.1 mg/L) before adenosine thallium-201 imaging. Adenosine was infused for 6 minutes at a rate of 140 micrograms/kg/min. Thallium-201 (2.5 to 3.0 mCi) was administered after 3 minutes of infusion. Blood pressure, heart rate, symptoms, and the electrocardiogram were monitored continuously. Planar thallium-201 imaging was obtained in three standard views and was interpreted using blinded segmental analysis and computerized quantitation. Systolic and diastolic blood pressure at baseline and during adenosine administration were similar following treatment with theophylline and placebo. The increase in heart rate observed during adenosine infusion was significantly reduced by theophylline pretreatment. Adenosine-induced symptoms (both cardiac and noncardiac) as well as ischemic electrocardiographic changes were significantly reduced after theophylline infusion (p < 0.05). In one patient, Mobitz type II heart block seen during adenosine infusion following placebo was absent with theophylline pretreatment. The size of adenosine-induced thallium-201 defects was unchanged by theophylline infusion using either segmental analysis (8 +/- 4 vs 9 +/- 5) or a computerized score (47 +/- 27 vs 45 +/- 21). Despite reduction in both symptoms and ischemic electrocardiographic changes, theophylline does not alter thallium-201 imaging following intravenous adenosine infusion.