Comprehensive model for simultaneous MRI determination of perfusion and permeability using a blood-pool agent in rats rhabdomyosarcoma

To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/ 13 ms/1.2 ms/60°) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume V_distribution, volume transfer constant K^trans, rate constant of influx k_pe, and initial extraction (fraction) E. Tumor perfusion was F=43±29 ml·min^–1·100 g^–1. The permeability study allowed the measurement of k_pe=0.37±0.12 min^–1 and K^trans=0.01±0.0031 min^–1. The blood volume could be assimilated to the distribution volume (V_distribution=2.9±1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34±1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization.     

Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min^–1 g^–1; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7±1.0 vs 3.6±1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9±0.9 (P<0.001) due to normalisation of maximal perfusion (2.3±0.5 ml min^–1 g^–1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH.     

Long-term cigarette smoking is associated with increased myocardial perfusion heterogeneity assessed by positron emission tomography

The pathophysiology of smoking-related coronary events in patients with normal coronary arteries is incompletely understood. This study was conducted to explore, in subjects without symptoms of cardiovascular disease, the long-term effects of smoking on regional coronary artery vasoactivity, especially during sympathetic stimulation. In ten smoking and ten non-smoking sex- and age-matched healthy volunteers, segmental myocardial perfusion was studied using dynamic parametric nitrogen-13 ammonia positron emission tomography at rest and during sympathetic stimulation evoked by the cold pressor stimulation. Smokers demonstrated a higher myocardial perfusion at rest (116±17 ml/min/100 g vs 96±20 ml/min/100 g,P <0.01) and an impaired myocardial perfusion increase during cold pressor stimulation (1.02±0.15 vs 1.18±0.17,P <0.05). The heterogeneity of perfusion, expressed as coefficient of variation, was significantly different between the smoking and the non-smoking group. The coefficient of variation of segmental myocardial perfusion was higher in smokers at rest (17.5%±4.2% vs 13.5%±1.9%,P <0.05) and during cold pressor stimulation (17.0%±3.2% vs 13.9%±1.8%,P <0.05). We conclude that the long-term effects of smoking in healthy volunteers are associated with (1) increased myocardial perfusion at rest, (2) impaired myocardial perfusion response to cold pressor stimulation, and (3) increased myocardial perfusion heterogeneity both at rest and during cold pressor stimulation. These results may suggest that in healthy subjects the longterm effect of smoking is related to abnormal coronary artery vasoactivity, presumably induced by an interplay of regional endothelial dysfunction and autonomic dysregulation.     

Relation of coronary vasoreactivity and coronary calcification in asymptomatic subjects with a family history of premature coronary artery disease

Electron-beam computed tomography (EBCT) allows non-invasive imaging of coronary calcification and has been promoted as a screening tool for coronary artery disease (CAD) in asymptomatic high-risk subjects. This study assessed the relation of coronary calcifications to alterations in coronary vascular reactivity by means of positron emission tomography (PET) in asymptomatic subjects with a familial history of premature CAD. Twenty-one subjects (mean age 51±10 years) underwent EBCT imaging for coronary calcifications expressed as the coronary calcium score (CCS according to Agatston) and rest/adenosine-stress nitrogen-13 ammonia PET with quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The mean CCS was 237±256 (median 146, range 0–915). The CCS was <100 in eight subjects and >100 units in 13. As defined by age-related thresholds, 15 subjects had an increased CCS (>75th percentile). Overall mean resting and stress MBF and CFR were 71±16 ml 100 g^–1 min^–1, 218±54 ml 100 g^–1 min^–1 and 3.20±0.77, respectively. Three subjects with CCS ranging from 114 to 451 units had an abnormal CFR (<2.5). There was no relation between CCS and resting or stress MBF or CFR (r=0.17, 0.18 and 0.10, respectively). In asymptomatic subjects a pathological CCS was five times more prevalent than an abnormal CFR. The absence of any close relationship between CCS and CFR reflects the fact that quantitative myocardial perfusion imaging with PET characterises the dynamic process of vascular reactivity while EBCT is a measure of more stable calcified lesions in the arterial wall whose presence is closely related to age.     

Demonstration of disturbed free fatty acid metabolism of myocardium in patients with non-insulin-dependent diabetes mellitus as measured with iodine-123-heptadecanoic acid

Myocardial free fatty acid metabolism and left ventricular function were evaluated in 15 middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 8 healthy control subjects. The study subjects had no evidence of coronary heart disease on the basis of clinical history, exercise ECG or myocardial perfusion scintigraphy. During peak exercise, iodine-123 hepatadecanoic acid (HDA) was intravenously injected. Myocardial activity distribution of ¹²³I-HDA was measured 10, 30, and 50 min after exercise using single-photon emission tomography (SPET); and then further corrected by free ¹²³I-iodine. Venous blood samples were drawn for detecting the plasma activity of ¹²³I. The net extraction of ¹²³I-HDA into the myocardium was obtained by dividing the corrected tissue ¹²³I concentration by the integral of the plasma time activity curve. The net extraction was 0.40 ± 0.06 min^–1 (mean ± SD) patients with NIDDM and 0.38 ± 0.06 min^–1 in control subjects (P>0.1), respectively. The faster elimination rate of ¹²³I-HDA was found in patients with NIDDM (0.029±0.008 min^–1) than in control subjects (0.022±0.004 min^–1; P<0.01). There was no statistically significant difference in left ventricular ejection fraction (LVEF) at rest between patients with NIDDM (53±9%) and control subjects (56±2%), whereas the increase of LVEF during exercise remained lower in patients with NIDDM (3.4±8.2%) than in control subjects (11.8±5.8%; P<0.025). A significant correlation (r=0.64; P < 0.01) was found between the net extraction of ¹²³I-HDA and the change of LVEF, as well as with exercise load (r=0.68; P<0.01). In conclusion, evidence of an increased fatty acid utilization and triglyceride synthesis rate was observed in the diabetic myocardium. Offprint requests to: J.T. Kuikka     

Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia

Purpose Tetrahydrobiopterin (BH₄) is an essential co-factor for the synthesis of nitric oxide (NO), and BH₄ deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH₄ deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia.Methods Myocardial blood flow (MBF; ml min^–1 g^–1) was measured at rest, during adenosine-induced (140 g kg^–1 min^–1 over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using ¹⁵O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH₄ (10 mg kg^–1 body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress.Results BH₄ increased exercise-induced hyperaemia in controls (2.96±0.58 vs 3.41±0.73 ml min^–1 g^–1, p<0.05) and hypercholesterolaemic subjects (2.47±0.78 vs 2.70±0.72 ml min^–1 g^–1, p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52±1.10 vs 4.85±0.45 ml min^–1 g^–1, p=NS) or hypercholesterolaemic subjects (4.86±1.18 vs 4.53±0.93 ml min^–1 g^–1, p=NS). Flow reserve utilisation remained unchanged in controls (70±17% vs 71±19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53±15% vs 66±14%, p<0.05).Conclusion BH₄ restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH₄ deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.The first two authors have contributed equally to the present project.An erratum to this article can be found at     

Left ventricular dysfunction during exercise in patients with angina pectoris and angiographically normal coronary arteries (syndrome X)

Left ventricular function during exercise and recovery was investigated in patients with angina pectoris, ST segment depression during exercise and angiographically normal coronary arteries (syndrome X) using a continuous left ventricular function monitor with cadmium telluride detector (CdTe-VEST). Fourteen patients with syndrome X and 14 patients with atypical chest pain without ST segment depression during exercise and normal coronary arteries (control group) performed supine ergometric exercise after administration of 740–925 MBq of technetium-99m labelled red blood cells, and left ventricular function was monitored every 20 s using CdTe-VEST. Left ventricular ejection fraction (EF) response was impaired (55% increase from rest to peak exercise) in 11 or 14 patients with syndrome X but in none of the control patients. Resting EF was similar in the two groups (62.1%±6.7% in patients with syndrome X, 61.9%±6.2% in controls); however, EF increase from rest to peak exercise was lower in syndrome X (–3.1±9.5% vs 14.7%±7.4%, P <0.001). After cessation of exercise, all patients showed rapid EF increase over baseline and this EF overshoot was lower (19.3%±8.3% vs 26.4%±7.3%, P <0.001) with the time to EF overshoot longer (114±43 s vs 74±43 s, P<0.05) in patients with syndrome X. Thus, in patients with syndrome X, left ventricular dysfunction was frequently observed during exercise in spite of normal epicardial coronary arteries. Correspondence to: J. Taki     

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (K_mono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min^–1 vs 0.065±0.015 min^–1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. K_mono in the right ventricular (RV) myocardium also increased (0.080±0.018 min^–1 vs 0.034±0.013 min^–1 at rest) (P<0.001), with an excellent correlation with the LV K_mono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects. Correspondence to: N. Tamaki     

Measurement of regional lower limb blood flow in normal humans by inhalation of 133Xe

A non-invasive method of measuring regional calf blood flow after inhalation of ¹³³Xe has been investigated. The mean blood flow at rest was 3.3 ml·min^-1·100 g tissue^-1 by the ¹³³Xe method and 3.5 ml·min^-1·100 g tissue^-1 by plethysmography. There was a significant correlation r=0.88, P<0.001. During exercise the mean blood flow in the anterior tibial compartment increased from 3.4 to 10.9 ml·min^-1·100 g tissue^-1 in ten cases and in the posterior compartment from 3.3 to 7.1 ml·min^-1·100 g tissue^-1 in seven cases as measured by the ¹³³Xe technique. The inhalation method seems to be an accurate, reliable and non-invasive method for measuring tissue blood flow in the human calf at rest and during exercise.     

Technetium-99m sestamibi myocardial tomography based on dipyridamole echocardiography testing in hypertensive patients with chest pain

The non-invasive diagnosis of coronary artery disease in hypertensives with chest pain is an important clinical concern because all exercise-dependent tests display limited feasibility and diagnostic accuracy; by contrast, dipyridamole echocardiography testing has been shown to have a similar feasibility and accuracy in hypertensive and normotensive subjects. The aim of this study was to evaluate the diagnostic capability of technetium-99m sestamibi tomography based on dipyridamole echocardiography testing in hypertensives with chest pain, and to compare the scintigraphic results with those of coronary angiography, exercise electrocardiography and dipyridamole echocardiography. Forty subjects with mild to moderate hypertension, chest pain and no previous myocardial infarction were submitted to^99mTc-sestamibi tomography (at rest and after high-dose dipyridamole echocardiography) and to exercise electrocardiography testing. At coronary angiography 22 patients (group A) had significant epicardial coronary artery disease (70% stenosis of at least one major vessel) and 18 normal main coronary vessels (group B). Dipyridamole^99mTc-sestamibi imaging was positive in 21/22 patients of group A and in 5/18 of group B. Dipyridamole echocardiography was positive in 18/22 patients of group A and in 5/18 of group B. Exercise electrocardiography was positive in 15/22 patients of group A and in 11/18 of group B. Four out of five subjects in group B with positive results in all the tests showed a slow run-off of angiographic contrast medium, probably due to small-vessel disease. Significant epicardial coronary artery disease in hypertensives with chest pain is unlikely when dipyridamole^99mTc-sestamibi tomography is negative. When scintigraphy is positive, either epicardial coronary artery disease or a small-vessel disease condition is possible. The association of scintigraphy with dipyridamole echocardiography testing allows the assessment of contractile function and myocardial perfusion by a single pharmacological stress.     

Larger perfusion defects with exercise compared with dipyridamole SPECT (exercise-dipyridamole mismatch) may reflect differences in epicardial and microvascular coronary dysfunction: When the stressor matters

Background Previous studies have reported larger myocardial perfusion defects with exercise as compared with dipyridamole. The aim of this study was to assess the hypothesis that this mismatch may reflect differences in epicardial and microvascular coronary vasomotor function. Methods and Results The response to intracoronary acetylcholine, nitroglycerin, and adenosine was studied in 36 patients with suspected angina and normal or near-normal coronary angiography findings who underwent both exercise and dipyridamole perfusion imaging. Of the patients, 27 (75%) had reversible defects with exercise (group I) and 9 had normal scans or nonreversible defects (group II). Repeated imaging with dipyridamole showed significant improvement or disappearance of perfusion defects in group I patients. The mean summed difference score (SDS) decreased from 5.52±3.19 with exercise to 1.11±1.60 with dipyridamole (P=.0001) in group I and did not change in group II. An abnormal epicardial response to acetylcholine, reflecting endothelial dysfunction, occurred in 93% of group I patients compared with only 33% of group II patients (χ², P=.002) and was significantly related to exercise SDS (r=0.49, P=.002) but not to dipyridamole SDS. By contrast, most patients showed normal epicardial and microvascular responses to the mainly non-endothelium-dependent vasodilators nitroglycerin and adenosine with no differences in coronary flow reserve between groups (2.91±0.72 vs 2.98±0.52, P=.79). Conclusions Exercise-dipyridamole perfusion mismatch may reflect differences in epicardial endothelial and microvascular dysfunction.     

Left bundle branch block and coronary artery disease: Accuracy of dipyridamole thallium-201 single-photon emission computed tomography in patients with exercise anteroseptal perfusion defects

Background  Reduced septal or anteroseptal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) even in the absence of left anterior descending (LAD) coronary artery disease. The purpose of this study was to evaluate prospectively the accuracy of dipyridamole²⁰¹TI single-photon emission computed tomography (SPECT) in detecting LAD coronary artery disease in patients with LBBB and septal or anteroseptal perfusion defects on exercise²⁰¹TI SPECT. Methods and Results  Twelve consecutive patients (10 men and two women) with complete LBBB and septal or anteroseptal perfusion defects on exercise²⁰¹TI SPECT underwent dipyridamole²⁰¹TI SPECT. The delay between dipyridamole and exercise was 2 to 30 days. Coronary angiography was performed during this period in all patients. Six (50%) of 12 patients with exercise perfusion defects showed normal perfusion after dipyridamole; all had normal coronary angiograms. The remaining six patients also had positive results of dipyridamole studies, two with moderate and four with severe septal or anteroseptal perfusion defects. Coronary angiography showed significant (>50%) LAD coronary artery stenosis in three patients; three patients with severe septal or anteroseptal perfusion defects after dipyridamole had normal coronary angiograms. Neither the evaluation of apical involvement nor the presence of dilated ventricles, decreased left ventricular ejection fraction, or wall motion abnormalities could help to identify (or explain) false-positive results. Conclusion  This study confirms that dipyridamole is more accurate than exercise in excluding LAD coronary artery disease. However, there are still false-positive results and the severity of the septal or anteroseptal perfusion defect does not add additional information to identify LAD coronary artery disease. Coronary angiography is thus necessary for positive dipyridamole study results to identify coronary artery disease as a major prognostic factor in patients with LBBB.     

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

Purpose Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means.Methods One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF 40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with ¹⁵O-labelled water (H₂¹⁵O) and ¹⁸F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (0.6 ml min^–1 g^–1) were classified as stunned, and segments with reduced MBF (<0.6 ml min^–1 g^–1) as hibernating if MRG was 0.25 mol min^–1 g^–1. Segments with reduced MBF and MRG <0.20 mol min^–1 g^–1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 mol min^–1 g^–1 as non-transmural scars.Results Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 mol min^–1 g^–1) and 233 (39%) reduced MRG (0.16±0.05 mol min^–1 g^–1). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 mol min^–1 g^–1) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min^–1 g^–1), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min^–1 g^–1 and 0.48±0.08 ml min^–1 g^–1, respectively), and lowest in transmural scars (0.40±0.14 ml min^–1 g^–1, P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40±0.19 mol min^–1 g^–1 vs 0.46±0.20 mol min^–1 g^–1, NS), and lowest in stunned myocardium with reduced MRG and transmural scars.Conclusion Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.     

Myocardial stunning induced and detected by adenosine stress perfusion imaging

Conclusion  Adenosine is a potent vasodilator that is thought to induce perfusion defects by causing heterogeneity in blood flow that consists of a large increase in flow through normal arteries and a smaller increase or no increase in flow through stenotic arteries.¹ As such, it is not supposed to induce true myocardial ischemia. However, vasodilator stress agents, such as adenosine and dipyridamole, can also cause “coronary steal,” in which the increased blood flow in a normal artery can actually siphon flow away from the bed distal to a highly stenotic lesion through collateral channels.¹ This might result in myocardial ischemia with secondary electrocardiographic changes and wall motion abnormalities. Exercise-induced myocardial stunning has been well recognized in the past.² However, vasodilator stress-induced myocardial stunning has only recently been reported with dipyridamole.³ Our case provides direct evidence that adenosine can induce true myocardial ischemia with secondary stunning, as illustrated by the persistent wall motion abnormality and the significant drop in ejection fraction detected 1 hour after the adenosine infusion. Thus the perfusion defects induced by adenosine are probably the result of a combination of heterogeneity in flow and true myocardial ischemia, presumably secondary to coronary steal.     

Changes in myocardial perfusion due to physical exercise in patients with stable coronary artery disease

Purpose Percutaneous transluminal coronary angioplasty (PTCA) is one of the main therapy options for patients with coronary artery disease (CAD), resulting in an improvement in myocardial perfusion and exercise capacity. Nevertheless, studies have also demonstrated a positive effect of regular exercise training on myocardial perfusion and maximum exercise capacity. The aim of this study was to evaluate changes in myocardial stress perfusion after 1 year of exercise training in comparison with the effects of PTCA in patients with CAD.Methods In 66 male patients with angiographically confirmed significant coronary artery stenosis in one target vessel, myocardial perfusion scintigraphy was performed at baseline and 12 months after randomisation into either a physical exercise group or a PTCA group. Circumferential count rate profiles in 16 wall segments were classified according to their relative count rate and localisation within or outside the area supplied by the stenosed vessel.Results Ischaemic segments showed a significant improvement in myocardial count rate within the target area after 12 months in both the PTCA and the training group (PTCA group: from 76.8±4.9% to 86.6±10.9%, p=0.03; training group: from 74.0±7.3% to 83.7±10.8%, p<0.01). Outside the target area only the training group showed a significant improvement (from 77.7±4.4% to 91.7±4.8%, p<0.01). Conclusion Our data indicate a significant improvement in stress myocardial perfusion in the training group after 12 months. The ischaemia is reduced not only in the target region of the leading stenosis but also in other ischaemic myocardial areas. In contrast, after PTCA stress perfusion improves only in the initially ischaemic parts of the target area.     

Myocardial blood flow and perfusion reserve in infarcted patients with stress-induced normalization of previously negative T waves: A positron emission tomography study

Background  The clinical correlations between stress-induced normalization of previously negative T waves (NTW) and regional myocardial blood flow (MBF) regulation and tissue viability remain debatable. Methods and Results  To confirm these correlations, 14 patients with previous anterior myocardial infarction (13 Q waves) and NTW on baseline electrocardiographic precordial leads and 10 healthy subjects were studied by means of positron emission tomography (PET). The MBF values were obtained in the anterior infarcted myocardial regions in either resting condition or during dipyridamole infusion, using N-13 ammonia as a flow tracer. Seven subjects had normalization of NTW (Group 1) and 7 had persistent NTW (Group 2) during dipyridamole infusion. The resting MBF values were similar for both Group 1 and Group 2 (0.43±0.13 versus 0.51±0.15 mL·min⁻¹.g⁻¹, respectively; P=not significant) and were significantly lower than in the anterior myocardial regions of healthy subjects (1.03±0.23 mL·min⁻¹.g⁻¹, P<.001). After administration of dipyridamole, the MBF was significantly higher in Group 1 than in Group 2 (0.88±0.37 versus 0.55±0.17 mL·min⁻¹.g⁻¹, respectively; P<.05) and markedly lower than in healthy subjects (3.78±0.64 mL·min⁻¹.g⁻¹, respectively; P<.05) and markedly lower than in healthy subjects (3.78±0.64 mL·min⁻¹.g⁻¹, P<.001). Coronary reserves (dipyridamole/resting MBF) were 2.03±0.40 and 1.14±0.44 in Group 1 and Group 2, respectively (P<.002). Conclusion  Despite similar values of resting perfusion, infarcted dysfunctional areas with or without NTW during stress may present different regional MBF responses; normalization of NTW demonstrates higher coronary flow reserve than persistent NTW, suggesting a better preserved coronary microcirculatory function in the former, indicative of the presence of myocardial viability. Presented in part at the 3rd International Congress on Nuclear Cardiology, Florence, April 1997.     

Altered myocardial perfusion during dobutamine stress testing in silent versus symptomatic myocardial ischaemia assessed by quantitative MIBI SPET imaging

The aim of the study was to compare the extent and severity of reversible underperfusion in silent versus painful myocardial ischaemia during the dobutamine stress test. A consecutive series of 85 patients with significant coronary artery disease and reversible perfusion defects on technetium-99m methoxyisobutylisonitrile single-photon emission tomography performed at rest and during high-dose dobutamine stress (up to 40 g kg^–1 min^–1) were studied. The left ventricle was divided into six segments. An ischaemic perfusion score was derived quantitatively by subtracting the rest from the stress defect score. Patients with multivessel disease had a higher ischaemic score (610±762 vs 310±411,P<0.05) and a higher number of reversible perfusion defects (2.1±1.2 vs 1.1±0.8,P<0.01) than patients with single-vessel disease. Typical angina occurred in 37 patients (44%) during the test. There was no significant difference between patients with and patients without angina with respect to age, gender, peak rate-pressure product, prevalence of previous myocardial infarction, diabetes mellitus, multivessel disease or number of stenotic coronary arteries. Stress, rest and ischaemic scores as well as the number and distribution of reversible defects were not different in patients with and patients without angina. Patients with angina more frequently had a history of typical angina before the test (43% vs 17%,P<0.01) and ST-segment depression during the test (54% vs 25%,P<0.01). It is concluded that in patients with coronary artery disease and ischaemia detected by dobutamine scintigraphy, the extent and severity of coronary artery disease and myocardial perfusion abnormalities are similar with or without angina during stress testing.     

Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a PET study of myocardial perfusion in diabetes.

Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing (CPT) with that of dipyridamole, a pharmacologic vasodilator, on coronary blood flow (CBF) measured by PET in NIDDM patients and healthy volunteers. In addition, we studied the effect of acute angiotensin-converting enzyme (ACE) inhibition on the flow response. METHODS: Ten NIDDM patients and 10 control subjects participated. Myocardial perfusion was determined at baseline, during CPT, and after dipyridamole infusion by PET using intravenous (13)N-ammonia. RESULTS: Resting CBF was similar in NIDDM patients and in control subjects. CPT increased CBF by 20% in the control group, whereas no increase was observed in the patients. After dipyridamole infusion, CBF increased 2- to 3-fold in patients and 3- to 4-fold in control subjects. The increase and maximal CBF were significantly higher in control subjects than in patients. During ACE-inhibitor infusion, which had no influence on resting CBF in patients or control subjects (n = 5), CPT increased CBF by 14% in the NIDDM group. After dipyridamole, CBF increased 3- to 4-fold in both groups. The increase in CBF and maximal CBF in the 2 groups were not different during ACE-inhibitor infusion. CONCLUSION: In these NIDDM patients without evidence of epicardial coronary disease, endothelial dysfunction is strongly suggested by an impaired increase in CBF both to dipyridamole and to CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE inhibition during CPT did induce significant increases in CBF in the patients, the changes during ACE inhibition were small compared with the dipyridamole response, and the absence of CBF increase during CPT in 3 of the 10 control subjects further limits the value of CPT for the study of coronary endothelial dysfunction.     

Time course of functional recovery after coronary artery bypass grafting surgery according to the preoperative reversibility of perfusion impairment on myocardial SPECT

Purpose Ischaemic myocardial dysfunction shows different time courses of functional recovery according to the pathophysiological characteristics of the dysfunction. In this study, we investigated the time course of functional recovery according to the preoperative reversibility of perfusion impairment on myocardial single-photon emission computed tomography (SPECT) after revascularisation surgery.Methods Forty-eight patients (42 men and 6 women; mean age 59±9 years) who underwent revascularisation surgery were included in the study. ²⁰¹Tl rest/dipyridamole stress ^99mTc-sestamibi gated SPECT was performed 10±8 days before (preoperative), 105±13 days after (early follow-up) and 497±66 days after (late follow-up) surgery. Using a 20-segment model, segmental perfusion and thickening were quantified with automatic software. As an indicator of the reversibility of perfusion impairment, a reversibility score (RevS) was defined as a measure of rest minus stress perfusion values. Segmental dysfunction and functional recovery were defined from quantified thickening values. Function-recovered segments were divided into early recovery and late recovery groups, and preoperative perfusion status was compared in these groups. Function-recovered segments were also re-classified into high-RevS and low-RevS groups according to the preoperative RevS, and the time courses of functional recovery were investigated in each group.Results A total of 502 segments were included in the analysis and 263 were finally classified as function-recovered segments. Of these, 172 were in the early recovery and 91 in the late recovery group. In terms of preoperative perfusion status, RevS was 8.9±10.8 in the early recovery group and 5.4±11.0 in the late recovery group (P=0.01). When all 502 segments were classified by RevS, no difference in the proportion of final function recovery was observed between the high-RevS and the low-RevS group (54% vs 51%). However, the proportion of early recovery was higher in the high-RevS group (73%) than in the low-RevS group (57%) (P=0.01).Conclusion Ischaemic dysfunctional myocardium with reversible perfusion impairment tends to recover function earlier after revascularisation surgery than myocardium with a persistent decrease in perfusion.     

Quantitative analysis of myocardial glucose utilization in patients with left ventricular dysfunction by means of 18F-FDG dynamic positron tomography and three-compartment analysis

Purpose Myocardial glucose utilization (MGU) is altered in various heart diseases. The aim of this study was to quantitatively assess regional myocardial glucose utilization in patients with left ventricular (LV) dysfunction by dynamic ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET).Methods A total of 18 subjects were studied, including ten with LV dysfunction (seven with idiopathic dilated cardiomyopathy and three with aortic regurgitation; NYHA II in 8 and III in 2) and eight healthy normal volunteers. Patients with diabetes mellitus were excluded. A dynamic PET study was performed for 40 min following the injection of 370 MBq of FDG after 50-g glucose loading. On the basis of a three-compartment model, MGU, K₁, k₂, and k₃ were computed on a pixel by pixel basis to generate LV myocardial parametric maps. FDG standardized uptake value (SUV) was also calculated using static images obtained 40 min after FDG injection. These metabolic values were compared with myocardial flow distribution (%Flow), LVEF, LV volumes, and LV wall thickening (WT) determined by gated myocardial single-photon emission computed tomography using QGS software in eight myocardial segments.Results MGU correlated positively with LV volumes and negatively with LVEF. K₁ was significantly higher in the segments of the patients than in those of the normal volunteers (0.082±0.055 vs 0.041±0.017 ml min^–1 g^–1, p<0.05), although there was no difference in MGU between the groups. On the other hand, SUV, k₂, and k₃ did not differ significantly between the groups. Among the patients, the K₁ values were significantly higher in the areas with impaired WT (%WT<17%) (0.109±0.063 vs 0.069±0.062 ml min^–1 g^–1, p<0.05) and in the areas with flow reduction (%Flow<71%) (0.112±0.076 vs 0.071±0.046 ml min^–1 g^–1, p<0.05).Conclusion These results indicate that glucose utilization was preserved in the patients with LV dysfunction, mainly due to an increase in glucose transport, particularly in the regions with severely impaired LV function. Thus, the quantitative assessment of myocardial glucose utilization by FDG dynamic PET may provide useful information for assessing the regional myocardial metabolic status in patients with LV dysfunction.