Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans.

OBJECTIVES: This study was performed to 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 micrograms/min and from 130 +/- 39% to 59 +/- 51% above control values (p < 0.001) at 40 micrograms/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.

Simultaneous measurement of coronary flow reserve by left anterior descending coronary artery Doppler and great cardiac vein thermodilution methods.

OBJECTIVES: The objective of this study was to compare left anterior descending coronary artery Doppler blood flow velocity and great cardiac vein thermodilution blood flow measurements of coronary flow reserve and submaximal coronary vasodilation in humans. BACKGROUND: Reported maximal coronary flow reserve values obtained with the coronary venous thermodilution method are lower than those obtained with other measurement methods. METHODS: Thermodilution measurements of great cardiac vein flow in 11 subjects were compared with simultaneous Doppler measurements of changes in left anterior descending coronary flow velocity after intracoronary administration of papaverine, nitroglycerin, iohexol and intravenous administration of dipyridamole. RESULTS: Coronary flow reserve (papaverine peak/rest flow ratio) was 3.7 +/- 1.7 (mean +/- SD) by the Doppler method and 2.0 +/- 0.7 by the thermodilution technique (p less than 0.001). Thermodilution flow changes were also smaller than Doppler-measured changes during submaximal vasodilation and during prolonged coronary dilation after dipyridamole administration. CONCLUSIONS: Coronary flow reserve and submaximal flow increases measured with the thermodilution method were consistently and substantially smaller than Doppler-derived measurements. This discrepancy has important implications for the comparison of coronary flow reserve measurements performed with the use of different techniques.

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)

Physiological assessment of sensitivity of noninvasive testing for coronary artery disease.

The sensitivity of three noninvasive tests for coronary artery disease was assessed by means of quantitative indexes of disease severity in three different groups of patients. The overall population consisted of 110 subjects with limited coronary artery disease and no myocardial infarction. Planar dipyridamole-201Tl scintigraphy was evaluated in 31 patients, computer-assisted exercise treadmill in 28, and high-dose dipyridamole echocardiography testing in 51. Sensitivity was assessed by rigorous gold standards to define disease severity, such as measurement of minimum cross-sectional area and percent area of stenosis, by quantitative computerized coronary angiography (Brown/Dodge method). On the basis of the results of previous studies, the presence of physiologically significant coronary artery disease was indicated by a stenotic minimum cross-sectional area (MCSA) of less than 2.0 mm2 or a greater than 75% area of stenosis. With MCSA as the gold standard, dipyridamole-201Tl scintigraphy, computerized exercise treadmill, and dipyridamole echocardiography testing showed sensitivities of 52%, 54%, and 61%, respectively, in the three different patient cohorts enrolled. With percent area of stenosis as the gold standard, the sensitivity figures obtained for dipyridamole-201Tl, computerized exercise treadmill, and dipyridamole echocardiography testing were 64%, 54%, and 69%, respectively. For each of the three tests, sensitivity increased with increasing lesion severity. Sensitivity was also better in patients with left anterior descending coronary (LAD) disease when compared with patients with left circumflex or right coronary artery disease. Results of these studies, which were obtained with more strict patient selection criteria and by more rigorous gold standards than previous studies, demonstrate that in patients with limited coronary artery disease none of the tests evaluated is definitely superior in sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphous ventricular tachycardia: a side effect of intracoronary papaverine.

Polymorphous ventricular tachycardia occurred in 1.3% of patients (5 of 391) who received intracoronary papaverine over a 47 month period. The arrhythmia lasted less than 1 min in all five patients, converting spontaneously in four and requiring electrical cardioversion in one. Ventricular tachycardia occurred in 4.4% of women (4 of 90) and 0.3% of men (1 of 301) (p less than 0.0025). Only one of the patients with ventricular tachycardia had coronary artery disease. To determine whether other clinical or procedural factors predispose patients to this side effect of papaverine, these 5 patients were compared with 25 control patients who were matched for gender and extent of coronary artery disease. The following variables were analyzed: age, baseline serum potassium and calcium levels, left ventricular ejection fraction, baseline heart rate, mean arterial pressure, corrected QT interval, the change in corrected QT interval produced by papaverine and the maximal dose of the drug per kilogram of body weight. Of these variables, only baseline heart rate differed significantly in the two groups of patients. Thus, polymorphous ventricular tachycardia is an infrequent, but important, side effect of papaverine that is usually self-limited. Women with a relatively slow heart rate appear to be predisposed to this side effect.