Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans.

OBJECTIVES: The objective of this study was to determine the effect of increases in heart rate and arterial pressure on maximal pharmacologic coronary blood flow reserve. BACKGROUND: Coronary flow reserve measurements are useful in assessment of the physiologic significance of coronary lesions. However, animal studies suggest that alterations in hemodynamic status may influence coronary flow reserve independent of coronary stenosis. METHODS: Coronary flow reserve was measured during cardiac catheterization with the use of a 3F coronary Doppler catheter and intracoronary papaverine. Flow reserve was measured under control conditions and during increases in heart rate produced by atrial pacing (18 patients) or during elevation of arterial pressure by intravenous phenylephrine infusion (9 patients) with intracoronary alpha-adrenergic blockade by phentolamine. RESULTS: Coronary flow reserve progressively decreased from 3.7 +/- 0.9 (mean +/- SD) at the rate of 71 +/- 8 beats/min at rest to 3.0 +/- 0.6 during pacing at 100 beats/min and to 2.6 +/- 0.5 during pacing at 120 beats/min. Flow reserve decreased because of a progressive increase in rest coronary flow velocity during pacing (122 +/- 16% of control value at 100 beats/min, 139 +/- 16% of control value at 120 beats/min), whereas papaverine hyperemia peak velocity remained unchanged. Flow reserve decreased with pacing tachycardia whether the initial flow reserve was normal or depressed. Mean arterial pressure increased from 95 +/- 12 mm Hg to 130 +/- 8 mm Hg during intravenous phenylephrine infusion and to 123 +/- 10 mm Hg during combined intravenous phenylephrine and intracoronary phentolamine infusions. Coronary flow reserve was not affected by the blood pressure increases (control value 4.3 +/- 1.0, phenylephrine 4.4 +/- 1.5, phenylephrine and phentolamine 4.4 +/- 2.0). CONCLUSIONS: Sudden increases in heart rate but not mean arterial pressure lead to a substantial reduction in maximal coronary blood flow reserve. These data suggest that the diagnostic utility of all flow reserve measurement techniques might be improved by standardization of heart rate during measurement or extrapolation of the measured flow reserve to that expected at a reference heart rate.

Sustained hemodynamic improvement during long-term therapy with levodopa in heart failure: role of plasma catecholamines.

Long-term therapy with oral sympathomimetic amines in patients with heart failure has been limited by the eventual development of diminished pharmacologic efficacy. However, a previous investigation in five subjects with heart failure suggested that long-term ingestion of levodopa, which is decarboxylated endogenously to dopamine, produces a sustained improvement in cardiac function. In the present study, levodopa was administered orally (1.5 to 2.0 g) to 14 patients with heart failure while hemodynamic responses and plasma catecholamines were monitored. Initially, an increase in cardiac index and stroke volume index was accompanied by a decline in systemic vascular resistance, mean pulmonary capillary wedge pressure and mean right atrial pressure. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose substantially after drug ingestion and correlated significantly with changes in cardiac index (r = 0.73, p less than 0.05). After 12 weeks of treatment with levodopa, the changes in cardiac index, stroke volume index, systemic vascular resistance and plasma dopamine levels persisted (n = 12 patients). Moreover, a significant decrease occurred in the heart rate at rest. Although there was an initial tendency for plasma norepinephrine concentrations to increase, a return to control levels was documented after long-term treatment. Thus, tolerance to the hemodynamic actions of levodopa did not develop during long-term administration of the drug. The hemodynamic responses observed can be ascribed to the activation of beta 1-adrenoceptors and dopamine1 receptors by dopamine generated from levodopa. The dopamine2 activity of dopamine does not appear to be responsible for the improvement in cardiac performance produced by levodopa.

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.

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.

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.

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)

Acute effect of cigarette smoking on the coronary circulation: constriction of epicardial and resistance vessels.

OBJECTIVES: This study was performed to determine the acute effect of cigarette smoking on proximal and distal epicardial conduit and coronary resistance vessels. BACKGROUND: Cigarette smoking causes constriction of epicardial arteries and a decrease in coronary blood flow in patients with coronary artery disease, despite an increase in myocardial oxygen demand. The role of changes in resistance vessel tone in the acute coronary hemodynamic effect of smoking has not been examined. METHODS: Twenty-four long-term smokers were studied during cardiac catheterization after vasoactive medications had been discontinued. The effect of smoking one cigarette 10 to 15 mm long on proximal and distal conduit vessel segments was assessed before and immediately after smoking and at 5, 15 and 30 min after smoking (n = 8). To determine the effect of smoking on resistance vessels, coronary flow velocity was measured in a nonobstructed artery with a 3F intracoronary Doppler catheter before and for 5 min after smoking (n = 8). Eight patients were studied without smoking to control for spontaneous changes in conduit arterial diameter (n = 5) and resistance vessel tone (n = 3). RESULTS: The average diameter of proximal coronary artery segments decreased from 2.56 +/- 0.12 mm (mean +/- SEM) before smoking to 2.41 +/- 0.09 mm 5 min after smoking (-5 +/- 2%, p < 0.05). Distal coronary diameter decreased from 1.51 +/- 0.07 to 1.39 +/- 0.06 mm (-8 +/- 2%, p < 0.01). Marked focal vasoconstriction after smoking was observed in two patients. Coronary diameter returned to baseline by 30 min after smoking. There was no change in vessel diameter in control patients. Despite a significant increase in the heart rate-mean arterial pressure product, coronary flow velocity decreased by 7 +/- 4% (p < 0.05) and coronary vascular resistance increased by 21 +/- 4% (p < 0.01) 5 min after smoking. There was no change in these variables in the control subjects. CONCLUSIONS: Smoking causes immediate constriction of proximal and distal epicardial coronary arteries and an increase in coronary resistance vessel tone, despite an increase in myocardial oxygen demand. These acute coronary hemodynamic effects may contribute to the adverse cardiovascular consequences of cigarette smoking.

Evaluation of diabetic patients for renal and pancreas transplantation: noninvasive screening for coronary artery disease using radionuclide methods.

Pharmacologic stress thallium scintigraphy is commonly performed in the risk assessment of diabetic patients with nephropathy before kidney and/or pancreas transplantation; however, controversy exists regarding the test's accuracy in detecting coronary artery disease. Our purpose was to compare pharmacologic stress thallium scintigraphy and also exercise radionuclide ventriculography with coronary angiography in diabetic patients undergoing evaluation for transplantation. In addition, we also determined the association of the test results with outcome after transplantation. The medical records of 47 patients (mean age, 37+/-9 years) without clinical evidence of coronary artery disease were reviewed. Forty-one patients had pharmacologic stress thallium scintigraphy performed during their evaluation. Sensitivity was 62% and specificity was 76% for detecting > or = 75% coronary artery stenosis (sensitivity was 53% and specificity was 73% for > or = 50% stenosis). Thirty-five patients had exercise radionuclide ventriculography performed. Sensitivity was 50% and specificity was 67% for detecting > or = 75% coronary artery stenosis (sensitivity was 44% and specificity was 63% for > or = 50% stenosis). Thirty patients had both pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography performed; when either test was abnormal, sensitivity in the detection of > or = 50% or > or = 75% stenosis tended to increase compared with pharmacologic stress thallium scintigraphy alone (0.05

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.

Stent-assisted coil embolization of complex wide-necked bifurcation cerebral aneurysms using the "waffle cone" technique. A review of ten consecutive cases.

Endovascular treatment of complex, wide-necked bifurcation cerebral aneurysms is challenging.  Intra/extra-aneurysmal stent placement, the "waffle cone" technique, has the advantage of using a single stent to prevent coil herniation without the need to deliver the stent to the efferent vessel. The published data on the use of this technique is limited. We present our initial and follow-up experience with the waffle cone stent-assisted coiling (SAC) of aneurysms to evaluate the durability of the technique. We retrospectively identified ten consecutive patients who underwent SAC of an aneurysm using the waffle cone technique from July 2009 to March 2011. Clinical and angiographic outcomes after initial treatment and follow-up were evaluated. Raymond Class I or II occlusion of the aneurysm was achieved in all cases with the waffle cone technique. No intraoperative aneurysm rupture was noted. The parent arteries were patent at procedure completion. Clinical follow-up in nine patients (median 12.9 months) revealed no aneurysm rupture. Two patients had a transient embolic ischemic attack at 18 hours and three months after treatment, respectively. Catheter angiography or MRA at six-month follow-up demonstrated persistent occlusions of aneurysms in seven out of eight patients. Another patient had stable aneurysm occlusion at three-month follow-up study. Our experience in the small series suggests the waffle cone technique could be performed on complex, wide-necked aneurysms with relative safety, and it allowed satisfactory occlusions of the aneurysms at six months in most cases.

Pulsatile spinal cord surrogate for intradural neuromodulation studies.

We have designed, built and tested a novel spinal cord surrogate that mimics the low-amplitude cardiac-driven pulsations of the human spinal cord, for use in developing intradural implants to be used in a novel form of neuromodulation for the treatment of intractable pain and motor system dysfunction. The silicone surrogate has an oval cross section, 10 mm major axis × 6 mm minor axis, and incorporates a 3 mm diameter × 3 cm long angioplasty balloon that serves as the pulsation actuator. When pneumatically driven at 1 Hz and 1.5 atmospheres (≈ 1140 mm Hg), the surrogate's diametric pulsation is ≈ 100 µm, which corresponds well to in vivo observations. The applications for this surrogate are presented and discussed.

Comparison of left anterior descending coronary artery hemodynamics before and after angioplasty.

Coronary artery disease (CAD) is characterized by the progression of atherosclerosis, a complex pathological process involving the initiation, deposition, development, and breakdown of the plaque. The blood flow mechanics in arteries play a critical role in the targeted locations and progression of atherosclerotic plaque. In coronary arteries with motion during the cardiac contraction and relaxation, the hemodynamic flow field is substantially different from the other arterial sites with predilection of atherosclerosis. In this study, our efforts focused on the effects of arterial motion and local geometry on the hemodynamics of a left anterior descending (LAD) coronary artery before and after clinical intervention to treat the disease. Three-dimensional (3D) arterial segments were reconstructed at 10 phases of the cardiac cycle for both pre- and postintervention based on the fusion of intravascular ultrasound (IVUS) and biplane angiographic images. An arbitrary Lagrangian-Eulerian formulation was used for the computational fluid dynamic analysis. The measured arterial translation was observed to be larger during systole after intervention and more out-of-plane motion was observed before intervention, indicating substantial alterations in the cardiac contraction after angioplasty. The time averaged axial wall shear stress ranged from -0.2 to 9.5 Pa before intervention compared to -0.02 to 3.53 Pa after intervention. Substantial oscillatory shear stress was present in the preintervention flow dynamics compared to that in the postintervention case.

Metabolic responses to exercise in patients with heart failure.

Metabolic and hemodynamic responses to exercise were evaluated in 10 patients with chronic congestive heart failure. We utilized an exercise protocol in which the work rate was increased continuously and oxygen uptake (VO2) kinetics were characterized by linear, first-order dynamics. VO2 at peak exercise (VO2max) was depressed at 12.8 +/- 2.3 ml/min/kg and the anaerobic threshold occurred at 63 +/- 10% of the VO2max. A significant correlation was observed between the VO2 at the anaerobic threshold and the resting cardiac index (r = .74, p less than .05). Ventilation-perfusion relationships improved during exercise, despite the presence of a widened alveolar-arterial gradient in oxygen tension and elevation of the physiologic dead space/tidal volume ratio. At peak exercise, a large breathing reserve (maximal voluntary ventilation-minute ventilation), a decline in arterial carbon dioxide tension, and a slight increase in arterial oxygen tension were observed. Plasma epinephrine levels at peak exercise correlated directly with VO2max (r = .74, p less than .05). Thus, although disturbances in ventilation-perfusion relationships occur in association with heart failure, exercise is not limited by an impairment in pulmonary function. The glycogenolytic action of epinephrine may play an important role in determining peak exercise capacity since glycogen stores are increasingly utilized at work rates above the anaerobic threshold.

Biphasic effect of nitroglycerin on coronary hemodynamics in normal subjects.

Coronary blood flow responses to nitroglycerin (NTG) in patients have been reported to be extremely variable. In dogs, NTG has a striking biphasic effect on coronary hemodynamics, consisting of a brisk increase followed by a decrease in coronary flow. To determine the effect of the drug on the coronary circulation in normal humans, NTG was injected I.C. (50 and 300 mcg) in 11 normals, and its effects on coronary flow velocity were compared to those of I. C. papaverine (6, 8, 10, and 12 mg) and saline (0.5 and 3.0 ml). Coronary flow velocity was measured using a 3F coronary Doppler catheter. The effect of each drug on coronary blood flow was analyzed in terms of both magnitude and duration (s) of the transient vasodilatory response following administration. Changes in coronary flow velocity (expressed as peak/resting velocity ratio) after 6, 8, 10, and 12 mg papaverine were (mean +/- SEM) 2.7 +/- 0.1, 3.4 +/- 0.3, 3.7 +/- 0.2, and 3.9 +/- 0.2, respectively. Very mild changes were observed with saline (1.3 +/- 0.1 and 1.7 +/- 0.1 after 0.5 and 3.0 ml, respectively), while ratios of 2.4 +/- 0.2 and 3.1 +/- 0.3 were obtained after NTG 50 and 300 mcg, respectively. The effect of 300 mcg NTG was significantly greater (p less than 0.01) than that of saline, 6 mg papaverine and 50 mcg NTG, lower than that of 12 mg papaverine and not significantly different from that of 8 and 10 mg papaverine. In terms of duration, the effect of 300 mcg NTG on coronary flow velocity was more prolonged than that of saline and 50 mcg NTG, and shorter than that of 6 to 12 mg papaverine.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial hemodynamic effects of oral levodopa in heart failure. Relation to the generation of dopamine.

Among the positive inotropic drugs available to improve myocardial contractility in congestive heart failure, only digitalis glycosides are suitable for oral administration. In this study, we administered oral levodopa (1.5 to 2.0 g), which is decarboxylated to form dopamine, to 10 patients with severe congestive heart failure. Peak hemodynamic responses occurred one hour after the ingestion of levodopa, with the mean (+/- S.E.M.) cardiac index increasing from 1.8 +/- 0.1 to 2.4 +/- 0.2 liters per minute per square meter of body-surface area (P less than 0.01) and systemic vascular resistance declining from 1905 +/- 112 to 1513 +/- 121 dyn X sec X cm-5 (P less than 0.01). These effects persisted for four to six hours. Left ventricular filling pressure, heart rate, and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose to a peak level of 34 +/- 5 ng per milliliter one hour after drug ingestion and decreased toward base line over the ensuing five hours. A significant correlation was observed between plasma dopamine levels and changes in cardiac index (r = 0.8; P less than 0.02). Five patients enrolled in a trial to evaluate the effectiveness of long-term therapy with levodopa had similar hemodynamic responses to the drug after 6.8 +/- 1.7 months of treatment. Thus, oral administration of levodopa to patients with severe heart failure produced a sustained improvement in cardiac function. The hemodynamic responses observed can be attributed to the activation of beta 1-adrenergic, dopamine, and dopamine receptors by dopamine derived from levodopa.

Effects of long-term therapy with oral ibopamine on resting hemodynamics and exercise capacity in patients with heart failure: relationship to the generation of N-methyldopamine and to plasma norepinephrine levels.

N-Methyldopamine (epinine), one of the few modifications of the dopamine (DA) molecule that retains agonist activity at the DA1 receptor, was administered orally as the diisobutyric ester, ibopamine (100, 200, and 300 mg), to 15 patients with congestive heart failure. An increase in cardiac index and decline in systemic vascular resistance was observed with each dose, and these hemodynamic effects persisted for 3 to 6 hr. Small transient increments in right atrial and pulmonary capillary wedge pressures occurred 0.5 hr after ingestion of 200 and 300 mg of ibopamine, but these pressures returned to baseline or lower levels within 30 min. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of epinine peaked 0.5 hr after administration of drug and then declined to minimal levels at 3 hr. Ten patients enrolled in a trial to evaluate the efficacy of long-term therapy with ibopamine; after 8 weeks of treatment, the initial hemodynamic responses to the drug were attenuated and no significant improvement in oxygen uptake at peak exercise was observed. A decline in plasma norepinephrine concentrations, which could be attributed to activation of alpha 2-adrenoceptors and/or DA2 receptors on sympathetic nerves, was observed after initial administration of ibopamine and persisted after long-term drug ingestion; no long-term hemodynamic benefit could be ascribed to the reduction in sympathetic activity.

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.