Does pharmacologic coronary flow reserve reflect vasodilator responsiveness to increased myocardial demand in humans?

OBJECTIVE: To assess the relationship between maximal pharmacologic coronary flow reserve and metabolic coronary vasodilation in nonstenotic coronary arteries. BACKGROUND: Evaluation of the coronary microcirculation in humans during cardiac catheterization is commonly performed by assessment of coronary hemodynamics during administration of potent coronary vasodilators. However, the relationship between maximal pharmacologic vasodilation and flow increases occurring in response to increased myocardial demand has not been evaluated. METHODS: The coronary blood flow responses to a maximally dilating dose of intracoronary adenosine or papaverine and to a standardized atrial pacing stress were assessed in 49 patients using intracoronary Doppler velocimetry. The blood flow responses to a maximally dilating dose of intracoronary adenosine and to intravenous infusion of dobutamine were determined in 13 patients. RESULTS: The maximal pharmacologic coronary flow reserve averaged 3.2 +/- 0.1 (mean +/- SEM). The coronary blood flow velocity increased by 32 +/- 3% during atrial pacing, and the change in coronary flow velocity was correlated with the change in the mean arterial pressure x heart rate product during pacing. Regression analysis revealed no relationship between the pharmacologic coronary flow reserve and the change in coronary flow velocity during atrial pacing or the response of the flow to pacing normalized with respect to the magnitude of stress reflected by the change in rate x pressure product. The coronary blood flow velocity increased by 135 +/- 16% during dobutamine infusion. Regression analysis revealed no relationship between the pharmacologic coronary flow reserve and the change in coronary flow velocity during dobutamine infusion. CONCLUSIONS: Knowledge of the maximal pharmacologic coronary flow reserve is an inadequate surrogate for assessment of coronary vasodilation in response to increases in myocardial metabolic demand in nonstenotic arteries.

The effect of aminophylline on pharmacological stress with intravenous adenosine.

Myocardial perfusion imaging with adenosine pharmacological stress may be useful in patients with obstructive lung disease who are unable to exercise. However, these patients are often treated with medications containing theophylline, which is an adenosine antagonist. This study assessed the effect of aminophylline on coronary vasodilation produced by intravenous adenosine as commonly used during cardiac imaging. Changes in coronary flow velocity (measured by intracoronary Doppler catheter) heart rate, arterial pressure and changes in coronary resistance were measured during intravenous infusion of adenosine at 140 micrograms/kg/min before and after aminophylline, 6 mg/kg intravenously in 12 patients. After aminophylline infusion, the theophylline level averaged 14 +/- 1 microgram/mL. The coronary hemodynamic effects of adenosine were markedly attenuated by aminophylline. Adenosine increased coronary blood flow velocity by 192 +/- 39% at control and 78 +/- 16% after aminophylline (P < .05 v control). Adenosine produced a 63 +/- 5% decrease in coronary vascular resistance at control and 40 +/- 6% (P < .05) after aminophylline. The utility of myocardial imaging techniques using coronary vasodilation with intravenous adenosine may be reduced in patients treated with theophylline-containing preparations.

Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus.

BACKGROUND: Structural and functional abnormalities of the coronary microcirculation have been reported in experimental diabetes mellitus. The purpose of this study was to evaluate coronary microvascular function in human diabetes. METHODS AND RESULTS: Twenty-four diabetic and 31 nondiabetic patients were studied during cardiac catheterization. A Doppler catheter or guidewire was used to measure changes in coronary blood flow velocity in a nonstenotic artery. Maximal coronary blood flow reserve was determined by using intracoronary adenosine or papaverine. Coronary dilation in response to an increase in myocardial metabolic demand was assessed by using rapid atrial pacing. Maximal vasodilator responses to papaverine and adenosine were compared in 12 diabetic patients. Maximal pharmacologic coronary flow reserve was depressed in diabetic (2.8 +/- 0.2, n = 19) compared with nondiabetic (3.7 +/- 0.2, n = 21, P < .001) patients. During atrial pacing, the decrease in coronary vascular resistance was attenuated in the diabetic (-14 +/- 3%) compared with the nondiabetic (-24 +/- 2%, P < .05) patients. Differences in coronary microvascular function between diabetic and nondiabetic patients were not attributable to differences in drug therapy, resting hemodynamics, or incidence of hypertension. In 12 diabetic patients the maximal coronary vasodilator responses to papaverine and adenosine were similar. CONCLUSIONS: This study demonstrates both reduced maximal coronary vasodilation and impairment in the regulation of coronary flow in response to submaximal increases in myocardial demand in patients with diabetes mellitus. These microvascular abnormalities may lead to myocardial ischemia in the absence of epicardial coronary atherosclerosis in some circumstances, and thus contribute to adverse cardiovascular events in diabetic patients.