Myocardial perfusion scintigraphy during maximal coronary artery vasodilation with adenosine

Pharmacologic coronary vasodilation as an adjunct to thallium-201 myocardial perfusion scintigraphy provides an important alternative form of stress that has been increasingly used in patients unable to perform an exercise stress test. Although dipyridamole has traditionally been used for this purpose, there are several compelling reasons why adenosine may be a preferable agent. First, dipyridamole acts by blocking the reuptake and transport of adenosine, which is the effective substance responsible for coronary vasodilation. Second, exogenous adenosine has a very short half-life (less than 2 seconds), which explains its very short duration of action as well as the brief, self-limiting duration of its side effects. Third, the adenosine infusion is controllable and may be increased or decreased as desired. Fourth, the coronary vasodilation induced by the doses of adenosine we recommend (140 micrograms/kg/min) may be more profound than that induced by the standard dipyridamole dose. Our experience to date, with nearly 1,000 patients studied, shows the adenosine thallium-201 test to be practical and well tolerated, with high sensitivity (87%) and specificity (94%) for detecting coronary artery disease.     

Adrenergic blockade blunts adenosine concentration and coronary vasodilation during hypoxia.

Myocardial hypoxia is thought to be an important stimulus for increasing interstitial adenosine concentration. The adenosine hypothesis of coronary control was investigated during steady-state hypoxia by making measurements of coronary venous and epicardial well adenosine concentrations in adrenergically intact dogs and in animals with alpha- and beta-receptor blockade. In the adrenergically intact group, hypoxia sufficient to lower coronary venous oxygen tension to 8 mm Hg increased coronary blood flow 243% from normoxic values. Both coronary venous and epicardial well adenosine concentrations were increased throughout the hypoxic period. In the adrenergically blocked group, hypoxia to a similar level of coronary venous oxygen tension produced an increase in coronary blood flow of only 75%, which was significantly less than in the adrenergically intact group (p less than 0.01). Coronary venous adenosine was only transiently elevated, and epicardial well adenosine was unchanged from control levels. In a separate group of alpha- and beta-receptor-blocked animals that received an infusion of L-homocysteine thiolactone during hypoxia, there was no difference in tissue S-adenosylhomocysteine levels compared with those of normoxic controls. It is concluded that much of the coronary vasodilation associated with systemic hypoxia is dependent on adrenergic activation and that adenosine may only play a role in sustained hypoxic vasodilation when adrenergic receptors are intact.     

Role of purines in acetylcholine-induced coronary vasodilation

Acetylcholine, when infused directly into the coronary arteries, increases coronary flow and stimulation of the vagus causes parasympathetic coronary vasodilation. Recent evidence suggests that this acetylcholine-induced relaxation of coronary resistance vessels is not the result of a direct effect on vascular smooth muscle cells, but rather involves endothelial cell mediated release of some unidentified substance(s) [5]. Possible candidates which may participate in this coupling are adenine nucleotides and adenosine. These purine compounds which act on the surface of coronary myocytes via specific receptors are powerful dilators of coronary vessels [3, 8, 11]. We report here that stimulation of cardiac muscarinic receptors by acetylcholine causes a marked increase in the release of ATP, AMP, and adenosine into the coronary system of isolated guinea-pig hearts independent of myocardial oxygen consumption. The amounts of adenosine liberated appear quantitatively sufficient to be causally involved in the coronary dilatory action of acetylcholine.     

Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise

Pharmacological coronary vasodilation induced by dipyridamole is often used in association with thallium-201 myocardial scintigraphy to evaluate the presence and prognostic significance of coronary artery disease. Because dipyridamole acts by blocking the cellular uptake of adenosine, we investigated the usefulness of direct intravenous administration of adenosine, a physiological substance with an exceedingly short (less than 2 seconds) plasma half-life, to induce maximal controlled coronary vasodilation in conjunction with 201Tl scintigraphy. We studied 89 patients (44 men and 45 women; mean age, 64 +/- 10 years [SD]) who were unable to perform an exercise test and were referred for evaluation of suspected coronary artery disease. The intravenous infusion of adenosine began at an initial rate of 50 micrograms/kg/min and was increased by stepwise increments every minute to a maximal rate of 140 micrograms/kg/min. 201Tl was injected intravenously after 1 minute at the highest infusion rate, followed by immediate and delayed (4 hour) tomographic imaging. At the highest infusion rate, adenosine induced a significant (p less than 0.001) decrease in systolic (8.7 +/- 19.3 mm Hg) and diastolic (6.7 +/- 9.4 mm Hg) blood pressures as well as a significant (p = 0.0001) increase in heart rate (14.5 +/- 11.0 beats/min). Side effects occurred in 83% of the patients but resolved spontaneously within 1 or 2 minutes after discontinuing the adenosine infusion. Chest, throat, or jaw pain were the most frequent symptoms and occurred in 57% of the patients. Headache (35%) and flush (29%) were also common. Ischemic electrocardiographic changes occurred in 12% of the patients, and transient first-degree atrioventricular block occurred in 10%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans

Objectives. This study was performed io assess the importance of adenosine in mediating metabolic coronary vasodilation during atrial pacing stress in humans.Background. Numerous animal studies have examined the role of adenosine in the regulation of coronary blood flow, with inconsistent results.Methods. The effect of the adenosine antagonist aminophylline (6 mg/kg body weight intravenously) on coronary functional hyperemia during rapid atrial pacing was determined in 12 patients. The extent of inhibition of adenosine vasodilation was assessed using graded intracoronary adenosine infusions before and after aminophylline administration in seven patients. Coronary blood flow changes were measured with a 3F intracoronary Doppler catheter.Results. After aminophylline administration, the increase in coronary flow velocity during adenosine infusions was reduced from 84 ± 48% (mean ± SD) to 21 ± 31% above control values (p < 0.001) at 10 μg/min and from 130 ± 39% to 59 ± 51% above control values (p < 0.001) at 40 μg/min. During rapid atrial pacing under control conditions, coronary blood flow velocity increased by 26 ± 16%. The flow increment during paced tachycardia after aminophylline (23 ± 10%) was unchanged from the control value, despite substantial antagonism of adenosine coronary dilation by aminophylline.Conclusions. These data suggest that adenosine does not play an important role in the regulation of coronary blood flow in response to rapid atrial pacing in humans.     

Comparison of coronary vasodilation with intravenous dipyridamole and adenosine.

Although both intravenous dipyridamole and adenosine have been used to produce coronary vasodilation during cardiac imaging, the relative potency of the commonly administered doses of these agents has not been evaluated. Accordingly, the coronary and systemic hemodynamic effects of intravenous adenosine (140 micrograms/kg per min) and intravenous dipyridamole (0.56 mg/kg over 4 min) were compared with a maximally dilating dose of intracoronary papaverine in 15 patients. Coronary blood flow responses were assessed using a Doppler catheter in a nonstenotic coronary artery. The protocol was discontinued in two patients because of transient asymptomatic atrioventricular (AV) block during adenosine infusion. The mean heart rate increased more with adenosine (11 +/- 9 beats/min) and dipyridamole (11 +/- 7 beats/min) than with papaverine (4 +/- 3 beats/min, p less than 0.05 vs. adenosine and papaverine). The mean arterial pressure decreased less with dipyridamole (-10 +/- 3 mm Hg) and papaverine (-9 +/- 4 mm Hg) than with adenosine (-16 +/- 5 mm Hg, p less than 0.01 vs. dipyridamole and papaverine). The peak/rest coronary blood flow velocity ratio was greater with papaverine (3.9 +/- 1.1) than with adenosine (3.4 +/- 1.2, p less than or equal to 0.05 vs. papaverine) or dipyridamole (3.1 +/- 1.2, p less than 0.01 vs. papaverine). A larger decrease in coronary resistance as measured by the coronary vascular resistance index occurred with papaverine (0.25 +/- 0.06) and adenosine (0.26 +/- 0.09) than with dipyridamole (0.31 +/- 0.10, p less than 0.01 vs. papaverine, p less than 0.05 vs. adenosine).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of adenosine in the maintenance of coronary vasodilation distal to a severe coronary artery stenosis. Observations in conscious domestic swine

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).     

Effect of adenosine triphosphate-sensitive potassium channel inhibitors on coronary metabolic vasodilation

The ATP-sensitive potassium (K(ATP)) channel is a distinct type of potassium ion channel that is found in the vascular smooth muscle cells of a variety of mammalian species, including humans. The activity of K(ATP) channels is determined by many factors including cellular ATP and ADP levels, thus providing a link between cellular metabolism and vascular tone through its effects on membrane potential. Experimental studies using inhibitors of K(ATP) channels, such as the sulfonuylurea class of drugs, indicate that these channels modulate coronary vascular tone including the hyperaemia induced by increased myocardial metabolism. This review examines the evidence linking K(ATP) channels to the regulation of coronary vascular tone and the potential clinical implications of pharmacologic therapies that act on K(ATP) channels.     

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement.     

The role of adenosine in prolonged vasodilation following flow-restricted exercise of canine skeletal muscle.

A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held constant at 12.5 +/- 1.3 ml/min per 100 g which was about 14% of the expected free flow for this exercise level. Skeletal muscle tissue adenosine was measured with the an enzymatic, spectophotometric assay of trichloroacetic acid extracts of congruent to 50 mg biopsy samples. Tissue adenosine rose from 2.30 +/- 0.90 nmol/g in resting muscle to 22.5 +/- 5.8 nmol/g by the end of the 22-minute exercise. Following exercise, tissue adenosine fell toward its baseline value with a time course very similar to the early portion of the return of skeletal muscle vascular resistance to its control level. Thus, skeletal muscle adenosine content (1) increases to a sufficient magnitude and (2) falls with an appropriate time course to be at least partly responsible for the early portion of prolonged vasodilation seen after flow-restricted exercise of skeletal muscle.     

Aged rat myocardium exhibits normal adenosine receptor-mediated bradycardia and coronary vasodilation but increased adenosine agonist-mediated cardioprotection

The purpose of this study was to determine whether aged myocardium exhibits decreased responsiveness to adenosine A1 and A(2a) receptor activation. Studies were conducted in adult (4-6 months) and aged (24-26 months) Fischer 344 x Brown Norway hybrid (F344 x BN) rats. Effects of the adenosine A1/A(2a) agonist AMP579 were measured in isolated hearts and in rats submitted to in vivo regional myocardial ischemia. Aged isolated hearts exhibited lower spontaneous heart rates and higher coronary resistance, as well as normal A1- and A(2a)-mediated responses. There was no difference in control infarct size between adult and aged rats; however, AMP579 treatment resulted in a 50% greater infarct size reduction in aged rats (18 +/- 4% of risk area) compared to adult rats (37 +/- 3%). These findings suggest that adenosine A1 and A(2a) receptor-mediated effects are not diminished in normal aged myocardium, and that aged hearts exhibit increased adenosine agonist-induced infarct reduction.     

Regional myocardial blood flow in man during dipyridamole coronary vasodilation

Regional myocardial blood flow before and after intravenous dipyridamole (0.56 mg/kg) was measured during cardiac catheterization in 11 patients using the 133Xe washout technique. Significant increases in heart rate (75 +/- 4 vs 87 +/- 6, p less than 0.004) and decreases in systolic blood pressure (144 +/- 8 vs 131 +/- 7, p less than 0.02) were observed with dipyridamole infusion. However, double product and cardiac output did not differ before or after drug infusion. Regional myocardial blood flow increased from 67 +/- 3 (SEM) to 117 +/- 3 ml/100 mg/min in myocardial segments supplied by nonobstructed coronary arteries. In stenotic coronary arteries, flow increased from 57 +/- 5 to 79 +/- 9 ml/100 mg/min with dipyridamole. We conclude that dipyridamole infusion results in flow differences which discriminate stenotic from nonstenotic coronary arteries.     

Role of left ventricle angioscintigraphy during exercise in the diagnosis of coronary disease. Comparison of static and dynamic exercise

The aim of this study was to compare the diagnostic value of exercise stress testing, Thallium 201 myocardial scintigraphy or after administration of dipyridamole and left ventricular angioscintigraphy performed either during a static (handgrip) or dynamic exercise (bicycle ergometry) for the positive diagnosis of stenosing coronary artery disease. The exercise angioscintigraphy was performed at equilibrium with 99m Tc red blood cell labelling. The global ejection fraction and that of seven radial segments of the left ventricle were measured, the data being recorded within a period of 2 minutes. The handgrip consisted in compressing a dynamometric ball at 1/3 maximal force for 3 minutes, with both hands; the ergometric exercise was increased by 30 Watt 2 minute increments until a positive ECG or 85% of the theoretical maximal heart rate for age was obtained. Normal subjects (n = 29) increased their global (+ 8%) and regional ejection fractions in each of the seven segments (p less than 0.05) during ergometric exercise: there was no significant change of global (-3% NS) or segmental ejection fractions during the handgrip exercise. In the coronary group (at least one greater than 70% stenosis) (n = 61) the fall in global ejection fraction was the same (-14%) with both forms of exercise; a similar fall in the segmental ejection fraction in the territory distal to the stenosis was observed with the handgrip (-22%) and bicycle ergometry (-28% NS). Dynamic exercise testing seemed superior to handgrip exercise. Therefore, the finding of an abnormal global ejection fraction on exercise (i.e. either a global ejection fraction less than the lower limit of normal on exercise, or lower than the global ejection fraction at rest), or of an abnormal regional ejection fraction (i.e. either a regional ejection fraction less than the lower limit of normal over at least 3 segments, or a regional ejection fraction on exercise lower than the regional ejection fraction at rest over at least 3 segments) detected coronary artery disease with a sensitivity of 94% and a specificity of 72%. Dynamic exercise angiography seemed to be more sensitive than maximal ECG stress testing (94% compared to 64%) more rapidly positive (p less than 0.05), as sensitive (94% compared to 83% NS) than Thallium myocardial scintigraphy, but less specific (72% compared to 90%, p less than 0.05), and as unspecific as ECG stress testing.(ABSTRACT TRUNCATED AT 400 WORDS)     

Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease

Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurements of coronary plasma and pericardial infusate adenosine concentrations during exercise in conscious dog: relationship to myocardial oxygen consumption and coronary blood flow

A conscious dog model was employed to evaluate the relationship among myocardial oxygen consumption (MVO2), myocardial adenosine release and coronary blood flow (CNF) during graded treadmill exercise. Two methods were utilized simultaneously as indexes of changes in interstitial adenosine concentrations, (1) a pericardial infusate technique and (2) to measurement of arterial-coronary sinus plasma adenosine concentration differences. Graded exercise was associated with graded increases in MVO2, CBF, pericardial infusate adenosine concentration (PI Ado) and adenosine washout in coronary plasma. Regression analysis demonstrated significant linear relationships for MVO2 v. CBF (r = 0.78, P less than 0.01), MVO2 v. PI Ado (r = 0.52, P less than 0.01), and PI Ado v. CBF (r = 0.76, P less than 0.01). Coronary plasma adenosine arterio-sinus differences, sinus plasma concentrations, and net washout of adenosine also increased with graded exercise, however, a significant inter-animal variance was noted. These data suggest that the plasma adenosine assay is capable of detecting directional (qualitative) changes associated with changes in cardiac metabolism, however, it may not be reliable as a quantitative indicator of interstitial adenosine concentrations due to multiple factors which may influence the plasma adenosine pool. The pericardial infusate technique, which presumably represents a model of diffusion, is relatively invariant by comparison. The results demonstrate a significant correlation among MVO2, PI Ado and CBF, and thereby provide support to the hypothesis that adenosine is a major factor in the coupling of myocardial oxygen demand to oxygen supply under physiological conditions.     

Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation

Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV). To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion). The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities. Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration. Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B). In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion. In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional capillary density in skeletal muscle during vasodilation induced by isoprenaline and muscular exercise

Functional capillary density in skeletal muscle was studied in an isolated, autoperfused preparation of the abdominal muscles of the rat during different forms of vasodilation. The macromolecule hydroxyethyl starch (MW 450,000), labeled with the fluorochrome lissamine-rhodamine B 200, was intravenously injected. When a certain volume of blood had passed the muscle the tissue was fixed by snap freezing. In histological sections those capillaries which had been perfused by the dye could be visualized in the fluorescence microscope. Increase in total muscular blood flow, measured by arterial drop counting, was induced by intraarterial infusion of isoprenaline and by muscular work (control 30.0 ± 2.6, isoprenaline 48.2 ± 4.4, postcontraction hyperemia 44.2 ± 7.4 ml/min × 100g). During hyperemia the functional capillary density (stained capillaries per muscle fiber) was affected in a different way: 0.81 ± 0.02 control, 0.71 ± 0.03 isoprenaline, and 0.93 ± 0.04 postcontraction hyperemia. The data support the view that a rise in total blood flow is not necessarily associated with an increase in functional capillary density.     

Role of endogenous adenosine in atrial fibrillation after coronary artery bypass graft

BACKGROUND: Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft (CABG). The mechanism of AF after CABG is not well defined; however, it is suggested that endogenous adenosine, released in response to tissue hypoxia, may play a mechanistic role in these arrhythmias. HYPOTHESIS: The purpose of this study was to examine whether intravenous theophylline, via adenosine A1 receptor antagonism, would correct or modify new-onset early (<48 h post CABG) atrial fibrillation in patients post CABG, and thereby implicate endogenous adenosine as an inciting agent. METHODS: A prospective double-blind, placebo-controlled study design was applied to 385 consecutive patients with coronary artery disease who had undergone CABG. Any patient who developed AF within 48 h of the operative procedure was randomly assigned to receive 5 mg/kg of intravenous theophylline (Group A) or matched intravenous placebo (Group B). The patients who converted to sinus rhythm within 15 min of drug administration were accepted as showing positive responses. RESULTS: Thirty patients comprised the study group. In Group A, 8 of the 15 patients (53%) converted from AF to sinus rhythm within 15 min of theophylline administration. One patient who converted to sinus rhythm 20 min after theophylline administration was accepted as showing a negative response. In the placebo-treated group, no patient converted to sinus rhythm within 15 min (p<0.007 compared with Group A). CONCLUSIONS: The mechanism of AF after CABG is not well defined and is probably multifactorial. However, this study demonstrated that antagonism of the adenosine A1 receptor can promptly convert many of these patients back to sinus rhythm, and thereby implicates endogenously released adenosine in a mechanistic role for inciting early (<48 h) post-CABG AF.