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Biomedical subjects

O Parodi

Publications and source records attributed to O Parodi.

At least 37 records · Page 2Linked to original sources

Comparative effects of enalapril and verapamil on myocardial blood flow in systemic hypertension.

BACKGROUND: The comparative effects of calcium channel blockers and ACE inhibitors on myocardial blood flow (MBF) in hypertensive patients after long-term treatment are still unknown. METHODS AND RESULTS: Twenty hypertensive subjects with normal coronary arteries were randomly assigned to verapamil 240 to 480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing tachycardia, and after dipyridamole by positron emission tomography and 13N-ammonia before and 6 months after treatment after 1 week of pharmacological washout. In both groups, blood pressure and heart rate during flow measurements were not different before and after therapy. Before treatment, mean MBF at rest, during pacing tachycardia, and after dipyridamole infusion was similar in the two groups; however, pacing and dipyridamole flows were significantly lower than those obtained in a control group of normotensive subjects. After treatment, in the enalapril-treated patients, MBF did not change in the three study conditions. In the verapamil-treated patients, MBF did not change at rest and significantly increased during pacing and after dipyridamole. The inhomogeneity of regional MBF distribution, evaluated from the coefficient of variation, decreased at rest after both treatments and, in the enalapril group, also during pacing. No relation was found between changes in MBF and changes in left ventricular mass. CONCLUSIONS: In arterial hypertension, MBF during pacing tachycardia and after dipyridamole is impaired. Successful therapy with verapamil increases MBF response to these stimuli, independent of changes in perfusion pressure and left ventricular mass. These results suggest that verapamil directly improves coronary microcirculatory function in hypertension. Enalapril does not significantly change MBF but reduces the inhomogeneity of regional flow distribution.

Antihypertensive Agents↗

Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease, a maximal vasodilation of the coronary microcirculation is generally assumed to occur during myocardial ischemia induced by rises in metabolic demand. However, vasoconstriction has been documented during severe prolonged ischemia in animals. The aim of this study was to investigate coronary vasomotor tone during pacing-induced ischemia in humans. METHODS AND RESULTS: The study included 11 patients with exercise-induced ischemia and single-vessel disease of the left anterior descending artery and 7 control subjects with normal coronary arteries. Blood flow velocity was monitored with a Doppler catheter in the left anterior descending artery. Coronary resistance index was calculated as the ratio between mean arterial pressure and flow velocity. Measurements were obtained at baseline, after intracoronary adenosine (2 mg), and during maximal atrial pacing in the absence and presence of adenosine. After adenosine administration at rest, coronary resistance decreased more in control subjects than in patients (25 +/- 7% of baseline versus 61 +/- 19%; P < .01). Coronary resistance decreased in all control subjects (P < .01) both at maximal pacing (60 +/- 17% of baseline) and after administration of adenosine during tachycardia (31 +/- 13% of baseline). By contrast, all 10 ischemic patients displayed increased coronary resistance at maximal heart rate (221 +/- 131% of baseline; P < .01 versus baseline, P < .01 versus control subjects). At this stage, adenosine decreased coronary resistance to 44 +/- 20% of values observed before injection. Additionally, it reduced ST-segment depression in 5 of 8 patients. CONCLUSIONS: In patients with coronary artery disease, transient myocardial ischemia induced by increased metabolic demand is not associated with maximal vasodilation. Rather, an inappropriate severe microvascular vasoconstriction is present that can be abolished by intracoronary adenosine.

Adenosine↗

Flow-function relation in patients with chronic coronary artery disease and reduced regional function. A positron emission tomographic and two-dimensional echocardiographic study with coronary vasodilator stress.

OBJECTIVES: We sought to elucidate the flow-function relation in chronic postischemic dysfunction during vasodilator stress. BACKGROUND: In patients with ischemia and regional dysfunction, stress echocardiography can elicit three responses in the dysfunctioning segments: no change, improvement or worsening. The physiology underlying these responses is unclear. METHODS: Seventeen patients with ischemia and left ventricular dysfunction underwent evaluation of regional function by two-dimensional echocardiography and myocardial blood flow by positron emission tomography and 13N-ammonia. Flow (ml/min per g) and function (regional wall motion score [RWMS] from 1 = normal to 4 = dyskinetic) were evaluated both at rest and after dipyridamole (0.56 mg/kg body weight over 4 min). RESULTS: In 45 normal segments, rest to dipyridamole flow increased from 0.83 +/- 0.22 (mean +/- 1 SD) to 1.87 +/- 0.90 (p < 0.01) with a hyperkinetic contraction pattern. Among dysfunctioning segments, responders (n = 11) showed an upsloping flow-function curve during stress (i.e., increased function [RWMS rest 2.5 +/- 0.5 vs. dipyridamole 1.2 +/- 0.4] and increased flow [rest 0.69 +/- 0.30 vs. dipyridamole 1.89 +/- 1.43, p < 0.01]); nonresponders (n = 20) had a flat flow-function curve during dipyridamole (i.e., fixed function [RWMS rest and dipyridamole 2.6 +/- 0.5] and no flow increase [rest 0.64 +/- 0.24 vs. dipyridamole 0.87 +/- 0.51, p = NS): Ischemic segments (n = 9) exhibited a downsloping flow-function curve during dipyridamole (i.e., worsened function [RWMS rest 2 +/- 0.5, dipyridamole 3.1 +/- 0.6] and no significant flow change [rest 0.67 +/- 0.29 vs. dipyridamole 0.79 +/- 0.23, p = NS]). CONCLUSIONS: Myocardial segments with rest dysfunction and a contractile reserve elicitable by a vasodilator stress more often exhibit residual flow reserve, whereas segments with a fixed or worsening mechanical response during stress show a flat flow response.

Aged↗

Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients.

BACKGROUND: Structural readaptation of systemic resistance-sized arterioles in response to an elevated blood pressure reduces the forearm vasodilator reserve in patients with essential hypertension. The development of a similar process at the coronary microvascular level has frequently been hypothesized, but little information about coronary remodeling during the uncomplicated stage of hypertension has been obtained, and the relationship with concomitant changes in forearm blood flow reserve is not known. OBJECTIVE: To assess the minimal myocardial resistance and its relationship with the minimal forearm resistance in a group of male patients with mild-to-moderate uncomplicated hypertension and carefully matched controls. MATERIAL AND METHODS: The minimal myocardial resistance (Rmin(myocardia), the mean arterial pressure: hyperemic myocardial flow ratio after administration of 0.84 mg/kg dipyridamole, measured by using positron emission tomography and [3N]-ammonia), minimal forearm vascular resistance (Rmin(forearm), a hemodynamic index of arteriolar structure derived from the mean blood pressure and maximal postischemic forearm blood flow by venous plethysmography), echocardiographic cardiac mass and wall thickness were measured in 25 male patients with mild-to-moderate uncomplicated essential hypertension, most of whom had previously been treated, and in seven sex- and age-matched normotensive controls. RESULTS: Rmin(myocardial) (and hyperemia: baseline myocardial flow ratios) did not differ significantly between the two groups, whereas Rmin(forearm) was significantly higher in hypertensives. There was no significant intra-individual correlation between the two parameters. The left ventricular mass index was greater in patients and was related previously to Rmin(forearm) but not to Rmin(myocardial) for the overall sample. In a subgroup analysis, Rmin(forearm) values were 2SD above control values in nine patients and within the normal range in the remaining 16. The myocardial reserve was very similar in the two subgroups. CONCLUSIONS: The myocardial vasodilator reserve appeared to be preserved in these mild-to-moderate uncomplicated hypertensive patients, whereas the forearm vasodilator capacity was reduced, suggesting that the hypertensive readaptation process was not distributed homogeneously over the two vascular beds.

Adaptation, Physiological↗

Lipomatous metaplasia in left ventricular scar.

BACKGROUND AND OBJECTIVE: Substitution of interstitial tissue by fat may be observed in the right ventricle of hearts but is less common in the left ventricle. Fat was noted in myocardial scars of patients undergoing heart transplantation, prompting this retrospective study to determine the frequency of left ventricular myocardial scar being replaced by fat and its significance METHODS AND RESULTS: The left and right ventricles and coronary arteries were sampled systematically and lesions quantified histologically in 97 normal subjects dying accidentally; 116 consecutive failing hearts excised at transplantation from patients with ischemic heart disease, idiopathic dilated cardiomyopathy or chronic valvulopathy; and 34 autopsy hearts of apparently normal subjects with "silent' Chagas' heart disease who died suddenly and unexpectedly. Twenty-two left ventricular aneurysmectomy specimens from ischemic patients with heart failure were also studied. Among excised hearts lipomatous metaplasia of myocardial scar was observed in 68% of ischemic heart disease, in 37% of chronic valvulopathy and in 26% of idiopathic dilated cardiomyopathy patients; it was seen in 15% of Chagasic patients and in 55% of aneurysm walls. CONCLUSIONS: Lipomatous metaplasia of scar is often associated with severe heart failure and is more frequent and extensive in ischemic heart disease. Transformation of a compact scar into compressible and "sliding' adipose tissue may worsen ventricular wall function, thus facilitating and/or aggravating aneurysm formation. This phenomenon must be considered in the evaluation of myocardial repair, cardiac imaging of viable myocardium, quantitative morphology of autopsy specimens, and qualitative and quantitative biochemical analysis of myocardial tissue.

Adipose Tissue↗

Temporal coding in vision: coding by the spike arrival times leads to oscillations in the case of moving targets.

The 'oscillations' which have been observed in the visual cortex of cats and monkeys in the case of moving targets are discussed in relation to a temporal coding based on the arrival times of spikes or bursts. A decoding process for this temporal coding is proposed in which neurons work in a correlator mode. In the case of motion analysis, periodic resetting is needed to avoid information jamming. This resetting is proposed to be responsible for the 'oscillations'. Good initial synchronization is required for the decoding process to be performed efficiently. A diffusive process based on interdendritic ionic currents is proposed and shown to operate efficiently, without any loss of spatial and temporal resolving powers.

Animals↗

Morphological bases for thallium-201 uptake in cardiac imaging and correlates with myocardial blood flow distribution.

To determine the morphological bases of thallium-201 myocardial distribution in chronic cardiac dysfunction and their relation to myocardial blood flow, myocardial slices from ten excised hearts of five chronic ischaemic heart disease patients and five idiopathic dilated cardiomyopathy patients, were imaged on a gamma camera to quantitate the uptake of thallium-201, injected 4 h before surgery, and myocardial blood flow from distribution of technetium-99m-labelled human albumin microspheres injected during surgery. Tracer distribution was correlated with histologically assessed myocardial fibrosis and myocytolysis. Thallium-201 uptake was inversely related to fibrosis (r = -0.73, in ischaemic heart disease, r = -0.65 in idiopathic dilated cardiomyopathy). In ischaemic heart disease, myocardial blood flow was related neither to thallium-201 uptake (r = 0.41) nor to the extent of fibrosis (r = -0.48). In this group, segments with normal or mildly reduced thallium-201 uptake showed significantly lower fibrosis than those with moderate or severe uptake defects (5 +/- 7% and 7 +/- 11% vs 33 +/- 14% and 42 +/- 12%, respectively, P < 0.0001. In a clinical model of chronic ischaemic dysfunction, despite severely depressed myocardial blood flow, extensive areas of myocardium devoid of significant structural impairment are present. Thallium-201 uptake effectively discriminates regions with preserved viability from those with relevant myocardial damage.

Adult↗

The role of coronary microvascular dysfunction in the genesis of cardiovascular diseases.

Positron emission tomography (PET) offers the unique capability of measuring specific flow (flow per unit of mass) in man by means of a regional, tridimensional, noninvasive approach. Using PET, myocardial perfusion abnormalities secondary to microvascular disorders have been investigated in arterial hypertension (AH), dilated and hypertrophic cardiomyopathy (CM), as well as in ischemic heart disease (CAD). In AH, regional perfusion at rest is within the normal range, while the coronary reserve and flow response to increase in metabolic demand are blunted. These flow abnormalities are independent of the degree of cardiac hypertrophy and the severity of AH; appropriate anti-ipertensive therapy is able to improve the perfusion abnormalities after long term treatment, independently of the effect on myocardial hypertrophy. Both dilated and hypertrophic CM demonstrate abnormal vasodilating capability, which has been shown to be present in the subclinical form of dilated DM; the reduction of coronary reserve is not related to the presence and extent of the hemodynamic impairment in dilated CM, and involves also nonhypertropied myocardium in asymmetric hypertrophic CM. These findings indicate a primary involvement of coronary microcirculation in non advanced forms of dilated and hypertrophic CM. Finally, in patients with CAD, myocardial territories supplied by angiographically normal coronary arteries show abnormal coronary reserve and flow during pacing tachycardia, indicating that, even in absence of epicardial coronary artery obstruction, microcirculation is impaired in subjects with coronary atherosclerosis. This abnormality can smooth perfusion differences between control and jeopardized regions. Accordingly, the absence of a perfusion defect during stress might indicate the presence of either a non significant stenosis or a diffuse impairment in microcirculatory function. Nuclear perfusion imaging with conventional perfusion tracers does not allow measurements of absolute blood flow, rather it provides an estimation of perfusion inhomogeneities. Although the agreement with the angiographic documentation of coronary artery disease has been frequently considered to characterize the diagnostic reliability of these techniques, the evaluation of myocardial perfusion provides an independent tool for the functional assessment of patient with heart disease. The possibility to obtain measurements of regional myocardial blood flow, provided by positron emission tomography, helps to identify the mechanisms affecting flow regulation in the myocardium. This tool thus provides a new rationale for the application of perfusion imaging, to obtain a more precise characterization of these patients, beyond the agreement with the morphological angiographic picture.

Arteriosclerosis↗

Thallium-201 reverse redistribution at reinjection imaging correlated with coronary lesion, wall motion abnormality and tissue viability.

UNLABELLED: Previous studies based on standard stress-redistribution 201TI scintigraphy provided conflicting results about the clinical significance 201Tl reverse redistribution. Recent observations indicate that the majority of these defects normalize following reinjection reflecting viable myocardium. METHODS: In this study, the meaning of reverse redistribution occurring at reinjection imaging, its relation to standard 4-hr redistribution, coronary lesion, abnormal wall motion and tissue viability were assessed. A region with normal activity in the stress image was considered as having reverse redistribution if 201Tl activity at reinjection imaging was definitely abnormal with a decrease in relative tracer uptake >15% of the peak. From a series of 270 patients, 29 showed reverse redistribution. Of these 29 patients, 27 had evidence of previous myocardial infarction. Coronary lesions were detected in all but 1 patient. Average ejection fraction was 0.38 +/- 0.11. RESULTS: On a segmental basis, 50/377 regions showed the pattern of reverse redistribution. A significant coronary lesion (> or = 50%) was found in 78% of these regions; occlusion rate was 50%, and collateral circulation was found in 35% of occluded vessels. Hypokinesis or akinesis was present in 72% of segments. Tissue viability, defined as an uptake >55% of the peak, was found in 44% of these segments. The 50 segments showing reverse redistribution were divided into two groups according to an abnormal uptake also at 4-hr redistribution (group 1, 25 segments) or appearing only following reinjection (group 2,25 segments). Despite segments of group 1 showing a higher degree of coronary stenosis (80 +/- 32 versus 59 +/- 43%, p < 0.01), a similar rate of coronary occlusion, ventricular dysfunction and maintained viability was found in the two groups. CONCLUSION: Reverse redistribution in chronic coronary artery disease is frequently associated with significant coronary lesion, collateral-dependent dysfunctioning myocardium and preserved tissue viability. The occurrence of reverse redistribution following reinjection expands the indication for viability imaging to all patients with known coronary artery disease and regional wall motion abnormalities who undergo diagnostic and prognostic 201TI scintigraphy.

Coronary Angiography↗

Value of transthoracic two-dimensional echocardiography in predicting viability in patients with healed Q-wave anterior wall myocardial infarction.

The role of transthoracic echocardiography as a predictor of recovery after revascularization has not yet been established. Two-dimensional echocardiography was performed in 15 patients with a healed anterior wall myocardial infarction and severe, isolated stenosis of the left anterior descending coronary artery before, and 3 to 6 months after angiographically confirmed successful revascularization. The asynergic segments were classified into 2 groups according to 2 different echocardiographic patterns: those showing a normal acoustic reflectance with normal end-diastolic thickness (pattern A segments) and those showing an increase in acoustic reflectance and reduced end-diastolic thickness (pattern B segments). We hypothesized that pattern A segments were more likely to recover (viable myocardium) and that pattern B segments were consistent with irreversibility. A total of 240 segments in the 15 patients were evaluated before and after revascularization. Sixty-seven segments were asynergic; of these, 52 were judged to have pattern A and 15 pattern B. Of the 52 pattern A segments, 27 were hypokinetic and 25 akinetic. All of the pattern B segments were akinetic (n = 9) or dyskinetic (n = 6). Pattern A was predictive of postoperative recovery in 39 of 52 segments (75%) (p < 0.0001); pattern B was predictive of irreversibly damaged tissue in 13 of 15 segments (87%) (p < 0.0001). Thus, in patients with healed anterior wall myocardial infarction, resting transthoracic echocardiography is a simple and reliable predictor of the behavior of asynergic segments after revascularization.

Adult↗

Myocardial blood flow response to pacing tachycardia and to dipyridamole infusion in patients with dilated cardiomyopathy without overt heart failure. A quantitative assessment by positron emission tomography.

BACKGROUND: Myocardial blood flow (MBF) impairment has been documented in advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to severe ventricular dysfunction, may limit myocardial perfusion. To assess whether MBF impairment in DCM may also be present independent of hemodynamic factors, the present study was designed to quantify myocardial perfusion in patients with mild disease without overt heart failure. METHODS AND RESULTS: Absolute regional MBF (milliliters per minute per gram) was measured by positron emission tomography and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in 13 healthy subjects. Patients were in New York Heart Association functional class I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg; range, 2 to 20 mm Hg). There were no differences in arterial blood pressure, heart rate, and rate-pressure product between patients and control subjects in the three study conditions. Compared with control subjects, DCM patients had lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P < .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min-1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/- 0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end-diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P < .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely depressed both at baseline and in response to stress. CONCLUSIONS: In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

Adult↗

Perfusional and metabolic effects of nisoldipine as shown by positron emission tomography after acute myocardial infarction.

After myocardial infarction, regional dysfunction can occur in viable myocardial regions because of the presence of baseline hypoperfusion. Recent evidence suggests that these areas may maintain a residual perfusion reserve. The aim of the present study was to evaluate whether oral nisoldipine can increase regional myocardial blood flow (MBF) in dyssynergic but viable myocardium after myocardial infarction. Patients with isolated left anterior descending coronary stenosis were studied 1 month after the first myocardial infarction. Patients underwent [18F]fluorodeoxyglucose imaging, and MBF was measured, using positron emission tomography and [13N]ammonia, at baseline and following dobutamine administration (10 micrograms/kg/min over 5 minutes). MBF measurements were repeated 24 hours after nisoldipine (10 mg twice daily). Preliminary results suggest that necrotic areas showed the largest reduction in baseline MBF. Dyssynergic-viable regions showed a reduced resting MBF but maintained a residual perfusion reserve in response to inotropic stimulation. Thus, nisoldipine selectively improved basal perfusion in dyssynergic-viable myocardium.

Adult↗

Microvascular dysfunction in collateral-dependent myocardium.

OBJECTIVES: The aim of this study was to evaluate myocardial blood flow regulation in collateral-dependent myocardium of patients with coronary artery disease. BACKGROUND: Despite great clinical relevance, perfusion correlates of collateral circulation in humans have rarely been estimated by quantitative methods at rest and during stress. METHODS: Nineteen patients with angina and isolated occlusion of the left anterior descending (n = 14) or left circumflex (n = 5) coronary artery were evaluated. Using positron emission tomography and nitrogen-13 ammonia, we obtained flow measurements at baseline, during atrial pacing-induced tachycardia and after intravenous administration of dipyridamole (0.56 mg/kg body weight over 4 min). Flow values in collateral-dependent and remote areas were compared with values in 13 normal subjects. RESULTS: Flow at rest was similar in collateralized and remote myocardium (0.61 +/- 0.11 vs. 0.63 +/- 0.17 ml/min per g, mean +/- 1 SD), and both values were lower than normal (1.00 +/- 0.20 ml/min per g, p < 0.01). During pacing, blood flow increased to 0.83 +/- 0.25 and 1.11 +/- 0.39 ml/min per g in collateral-dependent and remote areas, respectively (p < 0.05 vs. baseline); both values were lower than normal (1.86 +/- 0.61 ml/min per g, p < 0.01). Dipyridamole induced a further increase in perfusion in remote areas (1.36 +/- 0.57 ml/min per g, p < 0.01 vs. pacing) but not in collateral-dependent regions (0.93 +/- 0.37 ml/min per g, p = NS vs. pacing); again, both values were lower (p < 0.01) than normal (3.46 +/- 0.78 ml/min per g). Dipyridamole flow in collateral-dependent myocardium was slightly lower in patients with poorly developed than in those with well developed collateral channels (0.75 +/- 0.29 vs. 1.06 +/- 0.38 ml/min per g, respectively, p = 0.06); however, the former showed higher flow inhomogeneity (collateral/control flow ratio 0.58 +/- 0.10 vs. 0.81 +/- 0.22, respectively, p < 0.02). A linear direct correlation was observed between flow reserve of collateral-dependent and remote regions (r = 0.83, p < 0.01). CONCLUSIONS: Despite rest hypoperfusion, collateral-dependent myocardium maintains a vasodilator reserve that is almost fully utilized during increases in oxygen consumption. A global microvascular disorder might hamper adaptation to chronic coronary occlusion.

Adult↗

Residual coronary reserve identifies segmental viability in patients with wall motion abnormalities.

OBJECTIVES: The aim of this study was to determine whether the presence of residual coronary reserve can in itself identify viable segments. BACKGROUND: Experimental data suggest that despite hypoperfusion at rest, viable myocardium may exhibit persistence of coronary reserve. Preliminary observations in patients show that in basally dyssynergic areas, a residual vasodilator capability is present despite hypoperfusion at rest and that a flow-mediated increase in regional wall motion identifies residual viability. METHODS: Fourteen patients with evidence of previous myocardial infarction, infarct-related single-vessel coronary artery disease and impaired regional ventricular function at rest underwent positron emission viability imaging by fluorine-18 deoxyglucose. In addition, blood flow at rest and vasodilator capability were regionally evaluated in all patients by means of nitrogen-13 ammonia. RESULTS: Of a total of 252 segments, 133 were dyssynergic at rest. Of these 133 segments, 60 (group 1) showed normal metabolic activity and only mild reduction in myocardial blood flow. The other 73 segments showed a marked reduction in flow; of these, 25 (group 2, viable) had persistent metabolic activity, whereas 48 (group 3, necrotic) did not. Despite similar levels of hypoperfusion at rest, group 2 segments showed a preserved coronary reserve that was virtually absent in necrotic segments (2.6 +/- 1.3 vs. 1.3 +/- 0.5, p < 0.01). This value was similar to that observed in viable group 1 segments (2.5 +/- 1.6, p = NS). CONCLUSIONS: In addition to characterizing myocardium at risk, imaging of coronary flow at baseline and after dipyridamole by positron emission tomography provides helpful information on myocardial viability that may integrate the "static" viability information obtained with the baseline flow/metabolic approach.

Aged↗